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1.
Cancer Immunol Immunother ; 68(9): 1455-1465, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31444606

RESUMO

Macrophages have been shown to infiltrate a wide range of malignancies and are often considered to promote tumour survival, growth and spread. However, the source and behaviour of discrete tumour-associated macrophage populations are still poorly understood. Here we show a novel method for the rational development of bone marrow-derived monocytes appropriate for the study of processes which involve the contribution of circulating inflammatory monocytes. We have shown that in response to tumour-conditioned medium, these cells upregulate CD206 and CD115, markers traditionally associated with M2-type macrophages. Treated cells show reduced capacity for cytokine secretion but significantly impact CD4+ and CD8+ T-cell proliferation and polarization. Coculture with conditioned bone marrow-derived monocytes significantly reduced CD4+ T-cell proliferation but increased CD8+ T-cell proliferation and granzyme B expression with significant induction of IFNγ secretion by both CD4+ and CD8+ T cells, indicating that these cells may have a role in promoting anti-cancer immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Macrófagos/imunologia , Melanoma/imunologia , Monócitos/imunologia , Neoplasias Cutâneas/imunologia , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Técnicas de Cocultura , Meios de Cultivo Condicionados/metabolismo , Citocinas/metabolismo , Citotoxicidade Imunológica , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Lectinas de Ligação a Manose/metabolismo , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Receptores de Superfície Celular/metabolismo , Células Th2/imunologia
2.
Artigo em Chinês | MEDLINE | ID: mdl-31446716

RESUMO

Summary Allergic rhinitis(AR), a common and frequente disease, has attracted global attention in recent years. The imbalance between Th1 and Th2 cellular immune responses is the immunological basis of AR. Studies have found that vitamin D plays an important role in the occurrence of AR, and IL-33/ST2 is a newly discovered cytokine and signaling pathway in AR. There are certain specific associations between vitamin D and IL-33/ST2 in the pathogenesis of AR. This paper mainly analyzes the studies on the expression of vitamin D, IL-33/ST2 and Th1/Th2 cytokines in AR, so as to clarify the role of the above two factors in the pathogenesis of AR.


Assuntos
Interleucina-33/sangue , Rinite Alérgica/sangue , Vitamina D/sangue , Citocinas/sangue , Humanos , Células Th1/imunologia , Células Th2/imunologia , Vitaminas
3.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
4.
Environ Pollut ; 252(Pt B): 1519-1531, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277021

RESUMO

Some basic research has shown that nanomaterials can aggravate allergic asthma. However, its potential mechanism is insufficient. Based on the research that alumina nanopowder (nAl2O3) has been reported to cause lung tissue damage, the purpose of this study was to explore the relationship between nAl2O3 and allergic asthma as well as its molecular mechanism. In this study, Balb/c mice were sensitized with ovalbumin (OVA) to construct the allergic asthma model while intratracheally administered 0.5, 5 or 50 mg kg-1·day-1 nAl2O3 for 3 weeks. It was observed that exposure to nAl2O3 exacerbated airway hyperresponsiveness (AHR), airway remodeling, and inflammation cell infiltration, leading to lung function damage in mice. Results revealed that nAl2O3 could increase ROS levels and decrease GSH levels in lung tissue, promote the increases of the T-IgE, TGF-ß, IL-1ß and IL-6 levels, stimulate the overexpression of transcription factors GATA-3 and RORγt, decrease the levels of IFN-γ and IL-10 and increase the levels of IL-4 and IL-17A, resulting in the imbalance of Th1/Th2 and Treg/Th17 immune responses. In addition, antioxidant Vitamin E (Vit E) could alleviate asthma-like symptoms through blocking oxidative stress. The study displayed that exposure of nAl2O3 deteriorated allergic asthma through promoting the imbalances of Th1/Th2 and Treg/Th17.


Assuntos
Antioxidantes/farmacologia , Asma/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Vitamina E/farmacologia , Óxido de Alumínio/toxicidade , Animais , Asma/induzido quimicamente , Asma/imunologia , Interleucina-17/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Células Th2/imunologia
5.
Mol Immunol ; 112: 283-290, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31228660

RESUMO

Dehydroepiandrosterone (DHEA) has anti-inflammatory, anti-oxidant and immune-regulating properties, while the mechanism of DHEA actions remains unclear. The present study aims to investigate the effect and possible mechanism of DHEA on immune function of mice in vivo and in vitro. In vivo, a lipopolysaccharide (LPS)-induced experimental inflammation model was constructed to analyze the regulation of DHEA on anti-oxidative and immune function in ICR mice; In vitro, the effects of DHEA on the biological functions of lymphocytes and macrophages were studied. The results showed that DHEA increased the activity of total antioxidant capacity and superoxide dismutase, while it decreased the level of reactive oxygen species in LPS-induced mice. Meanwhile, DHEA increased the proportion of T lymphocytes and decreased that of B lymphocytes in primary cultured spleen lymphocytes, and markedly enhanced the Th1/Th2 ratio in spleen T lymphocytes. Furthermore, DHEA significantly increased the Th1 type cytokine (IL-2 and IFN-α) and decreased the Th2 type cytokine (IL-4 and IL-10) levels in LPS-induced mice or in primary cultured spleen T lymphocytes. In addition, DHEA improved the phagocytic ability, enhanced the NO production and increased the iNOS activity in peritoneal macrophages. Our data indicates that DHEA increases the macrophages function via improving NO content and up-regulating TNF-α expression levels; and it evoked a Th1 immuno-response and repressed a Th2 immuno-response through promoting a shift in Th1/Th2 balance toward Th1-dominant immunity in vivo and in vitro. These results provide substantial evidence on the mechanism of DHEA-mediated immune function and the efficient protection against infectious and inflammatory response in animals and humans.


Assuntos
Desidroepiandrosterona/imunologia , Animais , Antioxidantes/metabolismo , Citocinas/imunologia , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/imunologia , Óxidos de Nitrogênio/imunologia , Espécies Reativas de Oxigênio/imunologia , Baço/imunologia , Superóxido Dismutase/imunologia , Células Th1/imunologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/imunologia , Regulação para Cima/imunologia
6.
Int Arch Allergy Immunol ; 180(1): 10-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234191

RESUMO

BACKGROUND: Shrimp-derived allergen has a serious impact on people's health. Chitosan oligosaccharide (COS) has anti-allergic action but its function on shrimp allergen-induced allergy and related molecular mechanisms remain unclear. METHODS: COS and its degrees of polymerization (DP) were selected to interact with shrimp tropomyosin (TM) and IgE was measured. A mouse model of food allergy was established by receiving shrimp TM intraperitoneally. The models were treated with different concentrations of COS. Fecal and serum histamine, serum IgE, IgG1 and IgG2a, and inflammatory cytokines were measured. RESULTS: The main products for COS were DP2-6 with the contents of 6, 40, 26, 16, and 4%, respectively, and reacted with shrimp TM increasingly when COS DP was increased. Severe symptoms of food allergy were observed in the TM group (diarrhea, anaphylactic response, and rectal temperature). In contrast, COS treatment improved these symptoms significantly (p < 0.05). The sensitized mice were desensitized after they were treated with 1 mg/kg COS. COS treatment significantly reduced serum IgE and IgG1 levels, and increased IgG2a levels (p < 0.05). COS consumption decreased fecal and serum histamine. COS treatment reduced Th2 cytokine (IL-4, IL-5, and IL-13) levels and increased the Th1 cytokine (IFN-γ) level (p < 0.05). CONCLUSIONS: COS showed anti-allergy properties by regulating the levels of Th1 and Th2 cytokines.


Assuntos
Alérgenos/imunologia , Antialérgicos/farmacologia , Quitosana , Crustáceos , Hipersensibilidade Alimentar/imunologia , Oligossacarídeos/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Tropomiosina/imunologia , Animais , Antialérgicos/química , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Oligossacarídeos/química , Fenótipo , Células Th1/metabolismo , Células Th2/metabolismo
7.
Scand J Immunol ; 90(3): e12799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211854

RESUMO

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1ß, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1ß, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.


Assuntos
Doenças Autoimunes/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Pênfigo/imunologia , Plasma/imunologia , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/microbiologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Pênfigo/microbiologia , Plasma/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Células Th2/imunologia , Células Th2/microbiologia
8.
World J Microbiol Biotechnol ; 35(6): 91, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161259

RESUMO

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.


Assuntos
Bifidobacterium bifidum/fisiologia , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Probióticos/farmacologia , Animais , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Imunoglobulina G/sangue , Imunomodulação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Pulmão/imunologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Taxa de Sobrevida , Células Th1/imunologia , Células Th2/imunologia
9.
Parasit Vectors ; 12(1): 326, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253164

RESUMO

BACKGROUND: Helminths immunomodulate the host immune system by secreting proteins to create an inhibitory environment as a strategy for survival in the host. As a bystander effect, this balances the host immune system to reduce hypersensitivity to allergens or autoantigens. Based on this, helminth therapy has been used to treat some allergic or autoimmune diseases. As a tissue-dwelling helminth, Trichinella spiralis infection has been identified to have strong immunomodulatory effects; the effective components in the worm have not yet been identified. METHODS: The soluble extracts of T. spiralis adult worms and muscle larvae were used to treat airway inflammation before and after an ovalbumin (OVA)-sensitization/challenge in an OVA-induced asthma mouse model. The therapeutic effects were observed by measuring the level of inflammation in the lungs. RESULTS: The soluble products derived from T. spiralis parasites, especially from adult worms, were able to ameliorate OVA-induced airway inflammatory responses which were associated with reduced eosinophil infiltration, OVA-specific IgE, Th2 cytokine IL-4, and increased IL-10 and TGF-ß. The stimulation of the Treg response may contribute to the alleviated allergic inflammation. CONCLUSIONS: Trichinella spiralis worm extracts stimulate regulatory cytokines that are associated with reduced allergic airway inflammation. The identification of effective components in the adult worm extracts will be a crucial approach for developing a novel therapeutic for allergic and autoimmune diseases.


Assuntos
Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Extratos de Tecidos/imunologia , Trichinella spiralis/química , Animais , Antialérgicos/administração & dosagem , Antialérgicos/imunologia , Asma/induzido quimicamente , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Hipersensibilidade/prevenção & controle , Imunoglobulina E/sangue , Inflamação/prevenção & controle , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Células Th2/imunologia , Extratos de Tecidos/administração & dosagem , Trichinella spiralis/imunologia
10.
Appl Microbiol Biotechnol ; 103(12): 4977-4986, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037380

RESUMO

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Together, they caused most arthropod-borne diseases in the world. Previously, we had demonstrated that both live attenuated and inactivated JE vaccines elicited cross-protection against DENV infection, and a DNA vaccine candidate expressing JEV prM-E protein (named pCAG-JME) could provide effective protection against JEV infection in mice. In this study, we examined whether the same pCAG-JME could elicit cross-protection against DENV infection. Our results showed that pCAG-JME indeed induced cross-reactive antibodies and cross-protection against four different serotypes of DENV in mice. Interestingly, pCAG-JME-immunized mice also generated both Th1 and Th2 responses when stimulated by all four different serotypes of DENV antigens. Moreover, cross-primed CD8+ T cell response was also detected following the stimulation of DENV proteins using intracellular cytokine staining. In addition, sera from pCAG-JME-immunized mice significantly reduced the mortality caused by DENV2 infection in severe combination immunodeficiency mouse. These results suggest that both JE and DENV cross-reactive antibodies and cross-primed T cells might play important roles in the cross-protection. The findings of this study also indicate a possibility of developing novel multivalent genetically engineered vaccines against both JEV and DENV.


Assuntos
Antígenos Virais/imunologia , Proteção Cruzada , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Vírus da Encefalite Japonesa (Espécie)/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Vacinas contra Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/genética , Feminino , Imunização , Imunização Passiva , Camundongos , Camundongos Endogâmicos BALB C , Sorogrupo , Imunodeficiência Combinada Severa , Células Th1/imunologia , Células Th2/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética
11.
PLoS Negl Trop Dis ; 13(5): e0007436, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31120872

RESUMO

Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical symptoms and present a tightly regulated immune system characterized by higher frequencies of regulatory T cells (Treg), suppressed proliferation and Th2 cytokine responses accompanied with increased secretion of IL-10, TGF-ß and infection-specific IgG4. Nevertheless, the filarial-induced modulation of the host`s immune system and especially the role of regulatory immune cells like regulatory B (Breg) and Treg during an ongoing LF infection remains unknown. Thus, we analysed Breg and Treg frequencies in peripheral blood from Ghanaian uninfected endemic normals (EN), lymphedema (LE), asymptomatic patent (CFA+MF+) and latent (CFA+MF-) W. bancrofti-infected individuals as well as individuals who were previously infected with W. bancrofti (PI) but had cleared the infection due to the administration of ivermectin (IVM) and albendazole (ALB). In summary, we observed that IL-10-producing CD19+CD24highCD38dhigh Breg were specifically increased in patently infected (CFA+MF+) individuals. In addition, CD19+CD24highCD5+CD1dhigh and CD19+CD5+CD1dhighIL-10+ Breg as well as CD4+CD127-FOXP3+ Treg frequencies were significantly increased in both W. bancrofti-infected cohorts (CFA+MF+ and CFA+MF-). Interestingly, the PI cohort presented frequency levels of all studied regulatory immune cell populations comparable with the EN group. In conclusion, the results from this study show that an ongoing W. bancrofti infection induces distinct Breg and Treg populations in peripheral blood from Ghanaian volunteers. Those regulatory immune cell populations might contribute to the regulated state of the host immune system and are probably important for the survival and fertility (microfilaria release) of the helminth.


Assuntos
Anti-Helmínticos/administração & dosagem , Linfócitos B Reguladores/imunologia , Filariose Linfática/tratamento farmacológico , Filariose Linfática/imunologia , Interleucina-10/imunologia , Linfócitos T Reguladores/imunologia , Wuchereria bancrofti/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Animais , Filariose Linfática/genética , Filariose Linfática/parasitologia , Feminino , Gana , Humanos , Interleucina-10/genética , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Células Th2/imunologia , Adulto Jovem
12.
J Dermatol ; 46(7): 584-589, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087594

RESUMO

CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.


Assuntos
Quimiocinas CXC/sangue , Neovascularização Fisiológica/imunologia , Escleroderma Sistêmico/imunologia , Úlcera Cutânea/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Quimiocinas CXC/imunologia , Feminino , Dedos , Voluntários Saudáveis , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/patologia , Úlcera Cutânea/sangue , Úlcera Cutânea/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
13.
J Agric Food Chem ; 67(22): 6313-6323, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31070910

RESUMO

Gliadins are major allergens responsible for wheat allergies. Food processing is an effective strategy to reduce the allergenicity of gluten. In the present study, we determined the secondary and tertiary structures of gluten and gliadins treated by chemical, physical, and enzymatic means through FTIR, surface hydrophobicity, intrinsic fluorescence spectra, and UV absorption spectra. The results showed that the three treatments of phosphorylation and alcalase and papain hydrolyses significantly changed the conformational structures of gliadins, especially the secondary structure. Then, the potential allergenicity of the phosphorylated and alcalase and papain hydrolyzed gliadins were further characterized, and we observed a significant decrease in the allergenicity through the results of the index of spleen, serum total IgE, gliadin-specific IgE, histamine, and serum cytokine concentrations. An elevation of Th17 cells, the absence of Treg cells, and an imbalance in Treg/Th17 are associated with allergy. On the basis of the expression levels of related cytokines and key transcription factors, we also confirmed that phosphorylation and alcalase and papain hydrolysis could effectively reduce the allergenicity of gliadins by improving the imbalance of both Th1/Th2 and Treg/Th17 in the spleens of sensitized mice. This study suggested that the changes in conformational structure contribute to gliadin hyposensitization and that phosphorylation and alcalase and papain hydrolysis may be promising strategies for the production of wheat products with low allergenicity.


Assuntos
Gliadina/química , Gliadina/imunologia , Papaína/química , Subtilisinas/química , Hipersensibilidade a Trigo/imunologia , Alérgenos/química , Alérgenos/imunologia , Animais , Biocatálise , Histamina/imunologia , Humanos , Hidrólise , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Baço/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Triticum/química , Triticum/imunologia
14.
Medicine (Baltimore) ; 98(21): e15774, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124967

RESUMO

BACKGROUND: Melanoma-associated antigen-A (MAGE-A) was recognized as high-expressed in many solid tumors including esophageal carcinoma (EC), nevertheless, was reported to be low/not-expressed in normal tissues. Thus, it was considered as an extraordinary appropriate target for treatment especially in immunotherapy. Therefore, it demanded more detail knowledge on the precise function of MAGE-A. METHODS: In this study, we used the data from the Cancer Genome Atlas dataset (TCGA-ESCA) to analyze the expression and survival for MAGE A3/4/11 (the subtype of MAGE-A) using the online tool of UALCAN. Furthermore, the high-throughput sequencing data of the patients with esophageal squamous-cell carcinoma (ESCC) from TCGA dataset were performed to analyze the correlation test, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of MAGE A3/4/9/11 using LinkeDomics (online tool) and ClueGO (inner software of Cytoscape). Finally, relative gene expressions of MAGE A3/4/9/11 were verified by quantitative real-time PCR (q-PCR) in the patients with EC. RESULTS: MAGE A3/4/11 was high-expressed in tissues of patients with ESCC, and there was no difference in survival time for patients between the high-expressed with the low/medium-expressed. The Go enrichment analysis showed that the 4 MAGE-A subtypes (MAGE-A3/4/9/11) were enriched in the regulation of the adaptive immune response, translational initiation, interleukin-4 production, response to type I interferon, and skin development, respectively. The KEGG results showed that they were enriched in T cell receptor signaling pathway (MAGE-A3), Th1 and Th2 differentiation, antigen processing and presentation (MAGE-A4), cytokine-cytokine receptor interaction (MAGE-A9), and chemokine signaling pathway (MAGE-A11). CONCLUSION: MAGE A3/4/9/11 was high-expressed in EC, and were enrolled in the regulation of immune response. They may consider as candidate immune target for EC treatment and provided the messages for further research in the function of MAGE-A.


Assuntos
Antígenos de Neoplasias/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas de Neoplasias/genética , Imunidade Adaptativa/genética , Idoso , Antígenos de Neoplasias/imunologia , Biologia Computacional , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esôfago/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Células Th1/imunologia , Células Th2/imunologia
15.
Parasitol Res ; 118(6): 1849-1863, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055672

RESUMO

In the search for immunoprophylactics for the control of human lymphatic filariasis, we recently identified troponin 1 (Tn1) in Brugia malayi adult worms. The present study reports the cloning and expression of the B. malayi Tn1 (Tn1bm), its immunoprophylactic efficacy against B. malayi infection, and the immunological responses of the host. The Tn1bm gene was cloned (Acc no. JF912447) and expressed, and the purified recombinant Tn1bm (rTn1bm) presented a single ~ 27 kDa band. Parasite load in rTn1bm-immunized BALB/c mice challenged with B. malayi infective larvae (L3) was assessed. In rTn1bm-immunized animals, IgE, IgG, and IgG subclasses in the serum, cell proliferative response, Th1 and Th2 cytokine secretion (from splenocytes), and NO release (from peritoneal macrophages) were determined. Antibody-dependent cell-mediated cytotoxicity (ADCC) to L3 was assayed using rTn1bm-immune serum. The innate immune response markers MHC class-I, MHC class-II, TLR2, TLR4, and TLR6 expression in peritoneal macrophages and CD3+, CD4+, CD8+, and CD19+ in the splenocyte population were determined in Tn1bm-exposed cells from naïve mice. rTn1bm-immunized L3-challenged animals showed a 60% reduction in parasite burden. Immunization upregulated cellular proliferation, cytokine (IFN-γ, TNF-α, IL-1ß, IL-4, IL-6, and IL-10) secretion, NO release, and antigen-specific IgG, IgG1, and IgG2b antibody levels. rTn1bm-immune serum killed > 65% of L3 in the ADCC assay. Increased MHC class-II, TLR2, and TLR6 expression and the relative CD4+ and CD19+ cell populations of naïve animal cells indicated the ability of rTn1bm to mobilize innate immune responses. This is the first report of the immunoprophylactic potential of rTn1bm against B. malayi.


Assuntos
Anticorpos Antiprotozoários/sangue , Brugia Malayi/imunologia , Filariose Linfática/imunologia , Filariose Linfática/prevenção & controle , Troponina I/genética , Troponina I/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Brugia Malayi/genética , Clonagem Molecular , Citocinas/sangue , Citocinas/imunologia , DNA Complementar/metabolismo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Células Th1/imunologia , Células Th2/imunologia , Vacinação
16.
Int J Mol Sci ; 20(9)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31052382

RESUMO

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.


Assuntos
Células Dendríticas/imunologia , Doenças do Sistema Imunitário/imunologia , Células Th2/imunologia , Animais , Humanos , Doenças do Sistema Imunitário/terapia , Imunoterapia/métodos
17.
mSphere ; 4(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043512

RESUMO

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against C. jejuni strain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but only moderately immunogenic in humans when delivered alone or with aluminum hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), containing synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced similar amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+ IFN-γ+ IL-2+ TNF-α+ and CD4+ IL-4+ IL-10+ T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge with C. jejuni This study provides evidence that the ALF adjuvants may provide enhanced immunogenicity of this and other novel C. jejuni capsule conjugate vaccines in humans.IMPORTANCE Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Campylobacter/prevenção & controle , Imunogenicidade da Vacina , Lipídeo A/análogos & derivados , Saponinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lipídeo A/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Primatas , Células Th1/imunologia , Células Th2/imunologia , Vacinas Conjugadas/administração & dosagem
18.
Iran J Allergy Asthma Immunol ; 18(2): 163-172, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066252

RESUMO

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.


Assuntos
Fertilização In Vitro/métodos , Infertilidade Feminina/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Adulto , Biomarcadores , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Infertilidade Feminina/diagnóstico , Interleucina-17/metabolismo , Masculino , Prognóstico , Sêmen/metabolismo , Resultado do Tratamento
19.
Virchows Arch ; 475(1): 13-23, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31016433

RESUMO

T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/imunologia , Linfócitos do Interstício Tumoral/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Fatores de Transcrição Forkhead/análise , Fator de Transcrição GATA3/análise , Humanos , Imuno-Histoquímica , Imunofenotipagem/métodos , Antígeno Ki-67/análise , Metástase Linfática , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Fenótipo , Subpopulações de Linfócitos T/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Carga Tumoral , Microambiente Tumoral
20.
Immunity ; 50(4): 975-991, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995510

RESUMO

Asthma is a chronic inflammatory airway disease associated with type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13, which promote airway eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and immunogloubulin E (IgE) synthesis. However, only half of asthma patients exhibit signs of an exacerbated Type 2 response. "Type 2-low" asthma has different immune features: airway neutrophilia, obesity-related systemic inflammation, or in some cases, few signs of immune activation. Here, we review the cytokine networks driving asthma, placing these in cellular context and incorporating insights from cytokine-targeting therapies in the clinic. We discuss established and emerging paradigms in the context of the growing appreciation of disease heterogeneity and argue that the development of new and improved therapeutics will require understanding the diverse mechanisms underlying the spectrum of asthma pathologies.


Assuntos
Asma/imunologia , Citocinas/imunologia , Imunidade Adaptativa , Corticosteroides/uso terapêutico , Alérgenos/imunologia , Animais , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Asma/classificação , Asma/tratamento farmacológico , Asma/fisiopatologia , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Células Epiteliais/imunologia , Humanos , Inflamação/imunologia , Interferons/imunologia , Camundongos , Camundongos Knockout , Modelos Imunológicos , Células Th2/imunologia
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