Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.464
Filtrar
1.
Nat Immunol ; 22(10): 1316-1326, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34531562

RESUMO

Environmental allergens, including fungi, insects and mites, trigger type 2 immunity; however, the innate sensing mechanisms and initial signaling events remain unclear. Herein, we demonstrate that allergens trigger RIPK1-caspase 8 ripoptosome activation in epithelial cells. The active caspase 8 subsequently engages caspases 3 and 7, which directly mediate intracellular maturation and release of IL-33, a pro-atopy, innate immunity, alarmin cytokine. Mature IL-33 maintained functional interaction with the cognate ST2 receptor and elicited potent pro-atopy inflammatory activity in vitro and in vivo. Inhibiting caspase 8 pharmacologically and deleting murine Il33 and Casp8 each attenuated allergic inflammation in vivo. Clinical data substantiated ripoptosome activation and IL-33 maturation as likely contributors to human allergic inflammation. Our findings reveal an epithelial barrier, allergen-sensing mechanism that converges on the ripoptosome as an intracellular molecular signaling platform, triggering type 2 innate immune responses. These findings have significant implications for understanding and treating human allergic diseases.


Assuntos
Alérgenos/imunologia , Imunidade Inata/imunologia , Inflamação/imunologia , Adolescente , Animais , Caspase 8/imunologia , Linhagem Celular , Linhagem Celular Tumoral , Criança , Pré-Escolar , Citocinas/imunologia , Células Epiteliais/imunologia , Feminino , Células HEK293 , Humanos , Hipersensibilidade/imunologia , Interleucina-33/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transdução de Sinais/imunologia
3.
Elife ; 102021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550875

RESUMO

Background: Lack of early infection-exposure has been associated with increased allergy-related disease (ARD) susceptibility. In tropical Africa, little is known about which infections contribute to development of ARDs, and at which time. Methods: We used latent class analysis to characterise the early infection-exposure of participants in a Ugandan birth cohort and assessed ARDs in later childhood. Results: Of 2345 live births, 2115 children (90%) had data on infections within the first year of life while 1179 (50%) had outcome data at 9 years. We identified two latent classes of children based on first-year infection-exposure. Class 1 (32% membership), characterised by higher probabilities for malaria (80%), diarrhoea (76%), and lower respiratory tract infections (LRTI) (22%), was associated with lower prevalence of wheeze, eczema, rhinitis, and Dermatophagoides skin prick test (SPT) positivity at 9 years. Based on 5-year cumulative infection experience, class 1 (31% membership), characterised by higher probabilities for helminths (92%), malaria (79%), and LRTI (45%), was associated with lower probabilities of SPT positivity at 9 years. Conclusions: In this Ugandan birth cohort, early childhood infection-exposure, notably to malaria, helminths, LRTI, and diarrhoea, is associated with lower prevalence of atopy and ARDs in later childhood. Funding: This work was supported by several funding sources. The Entebbe Mother and Baby Study (EMaBS) was supported by the Wellcome Trust, UK, senior fellowships for AME (grant numbers 064693, 079110, 95778) with additional support from the UK Medical Research Council. LL is supported by a PhD fellowship through the DELTAS Africa Initiative SSACAB (grant number 107754). ELW received funding from MRC Grant Reference MR/K012126/1. SAL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609). HM was supported by the Wellcome's Institutional Strategic Support Fund (grant number 204928/Z/16/Z).


Assuntos
Doenças Transmissíveis/epidemiologia , Hipersensibilidade/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/imunologia , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Hipersensibilidade/prevenção & controle , Lactente , Recém-Nascido , Análise de Classes Latentes , Masculino , Prevalência , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Uganda/epidemiologia
4.
Front Immunol ; 12: 557433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566947

RESUMO

The occurrence of allergic diseases induced by aeroallergens has increased in the past decades. Among inhalant allergens, mites remain the important causal agent of allergic diseases. Storage mites- Tyrophagus putrescentiae are found in stored products or domestic environments. Major allergen Tyr-p3 plays a significant role in triggering IgE-mediated hypersensitivity. However, its effects on pulmonary inflammation, internalization, and activation in human epithelium remain elusive. Protease-activated receptors (PARs) are activated upon cleavage by proteases. A549 cells were used as an epithelial model to examine the PAR activation by Tyr-p3 and therapeutic potential of PAR-2 antagonist (GB88) in allergic responses. Enzymatic properties and allergen localization of Tyr-p3 were performed. The release of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK), and cell junction disruptions were evaluated after Tyr-p3 challenge. Enzymatic properties determined by substrate digestion and protease inhibitors indicated that Tyr-p3 processes a trypsin-like serine protease activity. The PAR-2 mRNA levels were significantly increased by nTyr-p3 but inhibited by protease inhibitors or GB88. Protease allergen of nTyr-p3 significantly increased the levels of pro-inflammatory cytokines (IL-6 and TNF-α), chemokine (IL-8), and IL-1ß in epithelial cells. nTyr-p3 markedly increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and MAP kinase. When cells were pretreated with GB88 then added nTyr-p3, the phosphorylated ERK1/2 did not inhibit by GB88. GB88 increased ERK1/2 phosphorylation in human epithelium cells. GB88 is able to block PAR-2-mediated calcium signaling which inhibits the nTyr-p3-induced Ca2+ release. Among the pharmacologic inhibitors, the most effective inhibitor of the nTyr-p3 in the induction of IL-8 or IL-1ß levels was GB88 followed by SBTI, MAPK/ERK, ERK, and p38 inhibitors. Levels of inflammatory mediators, including GM-CSF, VEGF, COX-2, TSLP, and IL-33 were reduced by treatment of GB88 or SBTI. Further, GB88 treatment down-regulated the nTyr-p3-induced PAR-2 expression in allergic patients with asthma or rhinitis. Tight junction and adherens junction were disrupted in epithelial cells by nTyr-p3 exposure; however, this effect was avoided by GB88. Immunostaining with frozen sections of the mite body showed the presence of Tyr-p3 throughout the intestinal digestive system, especially in the hindgut around the excretion site. In conclusion, our findings suggest that Tyr-p3 from domestic mites leads to disruption of the airway epithelial barrier after inhalation. Proteolytic activity of Tyr-p3 causes the PAR-2 mRNA expression, thus leading to the release of numerous inflammatory mediators. Antagonism of PAR2 activity suggests GB88 as the therapeutic potential for anti-inflammation medicine, especially in allergy development triggered by protease allergens.


Assuntos
Alérgenos/imunologia , Células Epiteliais Alveolares/imunologia , Hipersensibilidade/imunologia , Receptor PAR-2/antagonistas & inibidores , Células A549 , Acaridae/imunologia , Alérgenos/toxicidade , Células Epiteliais Alveolares/metabolismo , Animais , Humanos , Hipersensibilidade/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Proteínas de Insetos/imunologia , Proteínas de Insetos/toxicidade , Oligopeptídeos/farmacologia , Receptor PAR-2/imunologia , Mucosa Respiratória/imunologia
5.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445054

RESUMO

BACKGROUND: Restrictions due to the COVID-19 pandemic limited patients' access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). METHODS: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). RESULTS: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. CONCLUSIONS: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.


Assuntos
COVID-19/epidemiologia , Dieta , Hipersensibilidade/dietoterapia , Níquel/imunologia , Telemedicina/métodos , Adulto , Feminino , Hipersensibilidade Alimentar , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Qualidade de Vida , SARS-CoV-2/isolamento & purificação , Adulto Jovem
6.
Curr Opin Allergy Clin Immunol ; 21(5): 411-417, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334663

RESUMO

PURPOSE OF REVIEW: Anaphylactic reactions reported after Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA vaccines were expected to be more frequent in atopic subjects and attributed to its polyethylene glycol component. RECENT FINDINGS: Anaphylaxis to SARS-CoV2 RNA vaccines is no more frequent than in any vaccine and direct proofs for the role of its polyethylene glycol component are lacking. SUMMARY: Vaccines against coronavirus disease 2019 (COVID-19) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1 000 000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.


Assuntos
Anafilaxia/imunologia , Vacinas contra COVID-19/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Anafilaxia/epidemiologia , Animais , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Polietilenoglicóis/efeitos adversos , Caracteres Sexuais
7.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445142

RESUMO

It is difficult to treat allergic diseases including asthma completely because its pathogenesis remains unclear. House dust mite (HDM) is a critical allergen and Toll-like receptor (TLR) 4 is a member of the toll-like receptor family, which plays an important role in allergic diseases. The purpose of this study was to characterize a novel allergen, Der f 38 binding to TLR4, and unveil its role as an inducer of allergy. Der f 38 expression was detected in the body and feces of Dermatophagoides farinae (DF). Electron microscopy revealed that it was located in the granule layer, the epithelium layer, and microvilli of the posterior midgut. The skin prick test showed that 60% of allergic subjects were Der f 38-positive. Der f 38 enhanced surface 203c expression in basophils of Der f 38-positive allergic subjects. By analysis of the model structure of Der p 38, the expected epitope sites are exposed on the exterior side. In animal experiments, Der f 38 triggered an infiltration of inflammatory cells. Intranasal (IN) administration of Der f 38 increased neutrophils in the lung. Intraperitoneal (IP) and IN injections of Der f 38 induced both eosinophils and neutrophils. Increased total IgE level and histopathological features were found in BALB/c mice treated with Der f 38 by IP and IN injections. TLR4 knockout (KO) BALB/c mice exhibited less inflammation and IgE level in the sera compared to wild type (WT) mice. Der f 38 directly binds to TLR4 using biolayer interferometry. Der f 38 suppressed the apoptosis of neutrophils and eosinophils by downregulating proteins in the proapoptotic pathway including caspase 9, caspase 3, and BAX and upregulating proteins in the anti-apoptotic pathway including BCL-2 and MCL-1. These findings might shed light on the pathogenic mechanisms of allergy to HDM.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Dermatophagoides farinae/imunologia , Hipersensibilidade/imunologia , Ligação Proteica/imunologia , Receptor 4 Toll-Like/imunologia , Sequência de Aminoácidos , Animais , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pyroglyphidae/metabolismo , Testes Cutâneos/métodos
8.
Pan Afr Med J ; 38: 393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381537

RESUMO

Introduction: the relationship between asthma control and health-related quality of life (HRQoL) in adult asthmatics is fairly established, but the unique contribution of atopy to this relationship has received less attention. The aim of this study was to quantify the contribution of atopy to this relationship. Methods: in a cross-sectional study, we assessed HRQoL using mini-Asthma Quality of Life Questionnaire (AQLQ). Asthma control, atopy and lung function were assessed using the Asthma Control Test (ACT), skin prick test and spirometry respectively. Hierarchical multiple regression was used to examine the association between of HRQol and asthma control, atopy and other clinical and demographical factors. Results: eighty-two adult asthmatics (59 females), with median age of 44 years and median duration of asthma of 15 years were recruited from a tertiary hospital. Fifty-two (63%) were classified as atopic based on sensitization to at least one aeroallergen. The atopic individuals were younger and had better quality of life in activity domain; however, there was no significant difference between the atopic and non-atopic asthmatics in ACT score (19.0 vs 18.0) p=0.91, total AQLQ score (4.9 vs 4.6) p=0.22. The ACT scores correlated positively with total AQLQ scores [rho= 0.53, 95% Confidence Interval (CI) 0.35, 0.67; p< 0.001]. However, atopy contributed significantly to the emotional domain of HRQoL score, p=0.028. Conclusion: we concluded that better asthma control is associated with better quality of life and atopy contributed uniquely to emotional domain in health-related quality of life.


Assuntos
Alérgenos/imunologia , Asma/fisiopatologia , Hipersensibilidade/imunologia , Qualidade de Vida , Adulto , Fatores Etários , Asma/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Testes Cutâneos , Espirometria , Inquéritos e Questionários
9.
Front Immunol ; 12: 639008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394070

RESUMO

Background: Previous reports identified proteins associated with 'apoptosis' following cross-linking PrPC with motif-specific anti-PrP antibodies in vivo and in vitro. The molecular mechanisms underlying this IgG-mediated neurotoxicity and the role of the activated proteins in the apoptotic pathways leading to neuronal death has not been properly defined. Previous reports implicated a number of proteins, including apolipoprotein E, cytoplasmic phospholipase A2, prostaglandin and calpain with anti-PrP antibody-mediated 'apoptosis', however, these proteins are also known to play an important role in allergy. In this study, we investigated whether cross-linking PrPC with anti-PrP antibodies stimulates a neuronal allergenic response. Methods: Initially, we predicted the allergenicity of the epitope sequences associated with 'neurotoxic' anti-PrP antibodies using allergenicity prediction servers. We then investigated whether anti-PrP antibody treatment of mouse primary neurons (MPN), neuroblastoma cells (N2a) and microglia (N11) cell lines lead to a neuronal allergenic response. Results: In-Silico studies showed that both tail- and globular-epitopes were allergenic. Specifically, binding regions that contain epitopes for previously reported 'neurotoxic' antibodies such as ICSM18 (146-159), ICSM35 (91-110), POM 1 (138-147) and POM 3 (95-100) lead to activation of allergenic related proteins. Following direct application of anti-PrPC antibodies on N2a cells, we identified 4 neuronal allergenic-related proteins when compared with untreated cells. Furthermore, we identified 8 neuronal allergenic-related proteins following treatment of N11 cells with anti-PrPC antibodies prior to co-culture with N2a cells when compared with untreated cells. Antibody treatment of MPN or MPN co-cultured with antibody-treated N11 led to identifying 10 and 7 allergenic-related proteins when compared with untreated cells. However, comparison with 3F4 antibody treatment revealed 5 and 4 allergenic-related proteins respectively. Of importance, we showed that the allergenic effects triggered by the anti-PrP antibodies were more potent when antibody-treated microglia were co-cultured with the neuroblastoma cell line. Finally, co-culture of N2a or MPN with N11-treated with anti-PrP antibodies resulted in significant accumulation of NO and IL6 but not TNF-α in the cell culture media supernatant. Conclusions: This study showed for the first time that anti-PrP antibody binding to PrPC triggers a neuronal hypersensitivity response and highlights the important role of microglia in triggering an IgG-mediated neuronal hypersensitivity response. Moreover, this study provides an important impetus for including allergenic assessment of therapeutic antibodies for neurodegenerative disorders to derive safe and targeted biotherapeutics.


Assuntos
Anticorpos/imunologia , Hipersensibilidade/imunologia , Neurônios/imunologia , Proteínas PrPC/imunologia , Proteínas PrPC/metabolismo , Animais , Epitopos de Linfócito B/imunologia , Humanos , Camundongos , Neuroglia/imunologia
10.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445077

RESUMO

Honeybee venom is a source of proteins with allergenic properties which can result in in various symptoms, ranging from local reactions through to systematic life-threatening anaphylaxis, or even death. According to the World Allergy Organization (WAO), honeybee venom allergy is one of the most common causes of anaphylaxis. Among the proteins present in honeybee venom, 12 protein fractions were registered by the World Health Organization's Allergen Nomenclature Sub-Committee (WHO/IUIS) as allergenic. Most of them are highly immunogenic glycoproteins that cross-react with IgE and, as a consequence, may give false positive results in allergy diagnosis. Allergenic fractions are different in terms of molecular weight and biological activity. Eight of these allergenic fractions have also been identified in honey. This explains frequent adverse reactions after consuming honey in people allergic to venom and sheds new light on the causes of allergic symptoms in some individuals after honey consumption. At the same time, it also indicates the possibility of using honey as a natural source of allergen in specific immunotherapy.


Assuntos
Alérgenos/efeitos adversos , Venenos de Abelha/efeitos adversos , Hipersensibilidade/etiologia , Alérgenos/imunologia , Animais , Venenos de Abelha/imunologia , Abelhas/imunologia , Glicoproteínas/efeitos adversos , Glicoproteínas/imunologia , Humanos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Proteínas de Insetos/efeitos adversos , Proteínas de Insetos/imunologia
11.
Environ Toxicol Pharmacol ; 87: 103726, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418532

RESUMO

Epidemiological and experimental studies have shown that di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, can aggravate allergic diseases. DEHP promotes adaptive immune responses, although its effect on the innate immune system remains largely unknown. The present study investigated the effects of DEHP on group 2 innate lymphoid cells (ILC2) that produce Th2 cytokines in response to epithelial cell-derived cytokines, such as interleukin (IL)-33. ILC2 (lineage-negative, CD45.2+, Sca1+, KLRG1+) were isolated from the lungs of C57BL/6 J mice. Co-exposure to DEHP and IL-33 significantly increased IL-5 release from ILC2, whose level was higher than that of the vehicle and IL-33 alone. The effects of DEHP in the presence of IL-33 showed an inverted-U dose-response. The present is the first report showing that DEHP exacerbates allergy through the innate immune system.


Assuntos
Citocinas/imunologia , Dietilexilftalato/toxicidade , Imunidade Inata/efeitos dos fármacos , Interleucina-33/farmacologia , Linfócitos/efeitos dos fármacos , Plastificantes/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hipersensibilidade/imunologia , Interleucina-5/imunologia , Pulmão/citologia , Pulmão/imunologia , Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL
12.
Nutrients ; 13(8)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34444774

RESUMO

Multiple health benefits have been ascribed to brown seaweeds that are used traditionally as dietary component mostly in Asia. This systematic review summarizes information on the impact of brown seaweeds or components on inflammation, and inflammation-related pathologies, such as allergies, diabetes mellitus and obesity. We focus on oral supplementation thus intending the use of brown seaweeds as food additives. Despite the great diversity of experimental systems in which distinct species and compounds were tested for their effects on inflammation and immunity, a remarkably homogeneous picture arises. The predominant effects of consumption of brown seaweeds or compounds can be classified into three categories: (1) inhibition of reactive oxygen species, known to be important drivers of inflammation; (2) regulation, i.e., in most cases inhibition of proinflammatory NF-κB signaling; (3) modulation of adaptive immune responses, in particular by interfering with T-helper cell polarization. Over the last decades, several inflammation-related diseases have increased substantially. These include allergies and autoimmune diseases as well as morbidities associated with lifestyle and aging. In this light, further development of brown seaweeds and seaweed compounds as functional foods and nutriceuticals might contribute to combat these challenges.


Assuntos
Suplementos Nutricionais , Hipersensibilidade/dietoterapia , Inflamação/dietoterapia , Alga Marinha , Verduras , Imunidade Adaptativa , Ásia , Bases de Dados Factuais , Dieta , Alimento Funcional , Humanos , Hipersensibilidade/imunologia , Inflamação/imunologia , Obesidade , Espécies Reativas de Oxigênio
13.
Int J Mol Sci ; 22(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204710

RESUMO

Autophagy is a major self-degradative process through which cytoplasmic material, including damaged organelles and proteins, are delivered and degraded in the lysosome. Autophagy represents a dynamic recycling system that produces new building blocks and energy, essential for cellular renovation, physiology, and homeostasis. Principal autophagy triggers include starvation, pathogens, and stress. Autophagy plays also a pivotal role in immune response regulation, including immune cell differentiation, antigen presentation and the generation of T effector responses, the development of protective immunity against pathogens, and the coordination of immunometabolic signals. A plethora of studies propose that both impaired and overactive autophagic processes contribute to the pathogenesis of human disorders, including infections, cancer, atherosclerosis, autoimmune and neurodegenerative diseases. Autophagy has been also implicated in the development and progression of allergen-driven airway inflammation and remodeling. Here, we provide an overview of recent studies pertinent to the biology of autophagy and molecular pathways controlling its activation, we discuss autophagy-mediated beneficial and detrimental effects in animal models of allergic diseases and illuminate new advances on the role of autophagy in the pathogenesis of human asthma. We conclude contemplating the potential of targeting autophagy as a novel therapeutic approach for the management of allergic responses and linked asthmatic disease.


Assuntos
Asma/complicações , Asma/patologia , Autofagia , Hipersensibilidade/complicações , Hipersensibilidade/patologia , Animais , Asma/imunologia , Autofagia/genética , Humanos , Hipersensibilidade/imunologia , Inflamação/patologia , Modelos Biológicos , Transcrição Genética
14.
Mol Immunol ; 137: 238-246, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293591

RESUMO

GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.


Assuntos
Asma/imunologia , Proteína Relacionada a TNFR Induzida por Glucocorticoide/imunologia , Hipersensibilidade/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Pyroglyphidae/imunologia , Fatores de Necrose Tumoral/imunologia , Animais , Dermatophagoides pteronyssinus/imunologia , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Hipersensibilidade Respiratória/imunologia , Transdução de Sinais/imunologia
15.
Int Arch Allergy Immunol ; 182(9): 777-787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289474

RESUMO

BACKGROUND: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. OBJECTIVES: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. METHODS: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. RESULTS: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. CONCLUSIONS: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.


Assuntos
Alérgenos/imunologia , Células Dendríticas/imunologia , Mananas/imunologia , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Linfócitos T Reguladores/imunologia , Vacinas/imunologia , Alérgenos/administração & dosagem , Animais , Dessensibilização Imunológica , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Tolerância Imunológica , Imunização , Camundongos , Linfócitos T Reguladores/metabolismo
19.
Ann Allergy Asthma Immunol ; 127(3): 301-305, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34102303

RESUMO

OBJECTIVE: To review the literature and discuss a hypothesis as to why most people do not have allergy. This hypothesis is dependent on the following 3 main components: (1) airborne allergens (eg, from pollen or mites) are weak antigens that induce a B-cell response only in immunologically most reactive subjects (ie, with atopy); (2) a roadblock to production of immunoglobulin E (IgE) is the T helper 2/interleukin 4 requirement for class switch to IgE; (3) activated germinal centers prevent the formation of mature IgE-switched B-cells, creating a second roadblock to IgE production. DATA SOURCES: Transgenic reporter mice and a cross-sectional human cohort. STUDY SELECTIONS: From the mouse studies, we selected the data on histology and tissue-derived cell suspensions published by several groups in 2011 to 2014. From the human cohort, we selected our published microarray data on the levels of allergen-specific IgE and IgG in serum. RESULTS: The immune response to airborne atopic allergens entails both IgE and IgG antibodies rather than just an IgG or IgE response. However, as expected for an immune response without mature germinal centers, the specific IgG levels will be very low, typically in the ng/ml range. CONCLUSION: Control of IgE production is not just through the T helper 2/interleukin 4-mediated class switch. Recent studies suggest that mature germinal centers are likely to provide protection against the development of allergy to airborne allergens, as well. This may explain why allergen exposure does not induce allergen-specific IgE in everyone.


Assuntos
Centro Germinativo/imunologia , Hipersensibilidade/imunologia , Animais , Antígenos/imunologia , Linfócitos B/imunologia , Humanos , Imunoglobulina E/imunologia
20.
Med Clin North Am ; 105(4): 577-597, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059239

RESUMO

Severe cutaneous adverse reactions to medications (SCARs) include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. They are all non-immunoglobulin E mediated hypersensitivity reaction patterns, distinguished from simple cutaneous drug eruptions by immunologic pathogenesis and internal organ involvement. Herein the clinical features, diagnostic workup, and management considerations are presented for each of these major SCARs.


Assuntos
Pustulose Exantematosa Aguda Generalizada/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Eosinofilia/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/patologia , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Idoso , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Eosinofilia/induzido quimicamente , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Pessoa de Meia-Idade , Farmacogenética , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...