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1.
Artigo em Inglês | MEDLINE | ID: mdl-35564734

RESUMO

A medical anthropology research study was conducted in 2015 at the First Aid and Reception Center (CPSA) on the island of Lampedusa (Italy) as part of a larger health project carried out by the National Institute for Health, Migration and Poverty (INMP) in Rome. The study investigated the health conditions of migrants at the moment of their departure and on arrival, their migration journey, and their life plans and expectations for the future. The ethnographic method adopted for the study was based on participant observation and on data collection by means of a semi-structured interview (51 items simultaneously translated by cultural mediators into Tigrinya, Arabic, English, and French). Interviewed were 112 adults (82 men and 30 women) from the Gulf of Guinea and the Horn of Africa. The cooccurrence of forced migration and economic concerns was confirmed; violence and torture were constants throughout the migration journey in 81% of cases. Ethnographic data detailed the timing, countries, settings, perpetrators, and types of violence endured. A combination of qualitative and quantitative findings can both facilitate the identification of fragile health conditions and support clinicians in the diagnostic, therapeutic, and rehabilitation pathways. These data illustrate the importance and feasibility of multidisciplinary collaboration even in emergency contexts.

2.
J Leukoc Biol ; 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35199885

RESUMO

PI3K pathway plays a crucial role in dendritic cells (DCs) functions, as it regulates different cellular processes, such as maturation and cytokines production. However, the specific role of PI3K p110δ isoform in human DCs has not been thoroughly addressed. In this study, we analyze the effects of seletalisib, a potent and specific inhibitor of PI3K p110δ, on phenotype and antigen-presenting functions of monocyte-derived DCs undergone maturation via LPS. Seletalisib treatment reduced membrane HLA-DR as well as CD83 and CD40 costimulatory molecules, whereas CD80 and CD86 expression was only partially affected. Additionally, DCs cultures showed reduced TNF-α, IL-10, and IL-12 and increased IL-23 secretion levels. This resulted in a reduced capacity of DCs to prime allogeneic T cells, with a strong decrease of Th1 differentiation. On the other hand, PI3K p110δ inhibitor seletalisib increased CXCR4 and CCR7 expression and augmented the DCs migration toward CCL19 and CXCL12 ligands. At molecular level, inhibition of PI3K p110δ isoform by seletalisib significantly down-regulated the phosphorylation of AKT and other downstream signaling molecules, such as ribosomal protein S6, 4E-BP1, and NF-κB p65. In contrast, seletalisib did not affect p38 MAP kinase phosphorylation or TLR-associated adapter molecule TIRAP in DCs. Our results indicate that PI3K p110δ can serve as an important regulatory signal for DCs, and selective inhibition of PI3K p110δ isoform by seletalisib could be used for the prevention of exaggerated and harmful immune responses occurring in pathologic conditions, such as autoimmune disorders.

3.
Int J Soc Psychiatry ; 68(1): 203-209, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33438510

RESUMO

BACKGROUND: The effects of Sars-Cov-2 pandemic may increase vulnerability of migrants. AIMS: To investigate the effects of the governmental lockdown on the mental health of vulnerable migrants in treatment at an outpatient department. METHOD: In a telephone survey post-migration living difficulties and psychopathological symptoms were investigated, particularly post-traumatic thoughts and nightmares, anxiety, depression, feelings of tension and irritability, other sleep problems, as well as COVID-19 related fears. Psychopathological changes during the lockdown were detected and rated by clinicians. Rates of treatment discontinuation and reasons why were also recorded. RESULTS: Of 103 eligible patients, 81 answered the phone call and were included in the study. Mental symptoms were frequent but not as severe as expected. About 32% of patients in psychopharmacological treatment and almost 52% of patients in psychotherapy had discontinued treatment. Patients who were globally considered to have worsened if compared to their pre-coronavirus mental health conditions had in fact higher scores on several mental symptoms but mild specific fears about coronavirus issues, similar to those of patients improved or stable. Worsening was significantly associated with unemployment, lack of VISA, and treatment discontinuation. Shifting the way of providing psychotherapy into a web-based modality was significantly more frequent in stable/improved patients. CONCLUSION: Findings suggest that concrete life problems and treatment discontinuation more than the coronavirus fear, have predominantly affected the mental health conditions of our patients.


Assuntos
COVID-19 , Transtornos Mentais , Migrantes , Controle de Doenças Transmissíveis , Humanos , Transtornos Mentais/terapia , Saúde Mental , Pacientes Ambulatoriais , SARS-CoV-2 , Fatores Socioeconômicos
4.
Biomedicines ; 9(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34944746

RESUMO

Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected. Thereafter, we isolated TILs from seven freshly surgically removed melanomas and from three basal cell carcinomas (BCC), as a comparison with a non-melanoma skin cancer known to retain a high amount of Th17 cells. In both studies, we found that, differently from BCC, melanoma samples showed a lower percentage of Th17 lymphocytes. Additionally, TIL clones could not be induced to differentiate towards the Th17 phenotype in vitro. The presence or absence of Th17 cells did not correlate with any patient characteristics. We only observed a lower amount of Th17 cells in samples from woman donors. We found a tendency towards an association between expression by melanoma cells of placenta growth factor, angiogenic factors able to induce Th17 differentiation, and presence of Th17 lymphocytes. Taken together, our data indicate the necessity of a deeper analysis of Th17 lymphocytes in cutaneous melanoma before correlating them with prognosis or proposing Th17-cell based therapeutic approaches.

5.
Can J Infect Dis Med Microbiol ; 2021: 3068690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426755

RESUMO

BACKGROUND: Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. OBJECTIVES: The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. METHODS: Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. RESULTS: Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001). CONCLUSIONS: Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify "false" inactive carriers.

6.
Cells ; 10(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206914

RESUMO

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.


Assuntos
Inflamação/imunologia , Inflamação/patologia , Queratinócitos/patologia , Linfócitos T/imunologia , Apresentação do Antígeno/imunologia , Biomarcadores/metabolismo , Comunicação Celular , Proliferação de Células , Forma Celular , Microambiente Celular , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Queratinócitos/ultraestrutura , Modelos Biológicos , Pele/imunologia , Pele/patologia , Solubilidade , Linfócitos T/ultraestrutura
7.
Artigo em Inglês | MEDLINE | ID: mdl-33271775

RESUMO

Immigrants show higher adjusted diabetes prevalence than Italians, especially among South-East Asians followed by North and Sub-Saharan Africans. Diabetes progression is influenced by food behaviors, and diet control is a critical aspect in disease management. Food habits have many cultural and symbolic implications. Guidelines recommend that every patient should receive appropriate self-management education according to cultural and socioeconomic characteristics. This study aims to test whether a customized diet and transcultural mediator's support can improve immigrants' food habits. A pre-post quali-quantitative study was conducted among 20-79-year-old Bangladeshi and North African diabetic immigrants. The INMP transcultural mediator, an expert in the social and health care field, actively participates in clinical activity by decoding linguistic and cultural needs expressed by the foreigner patient. Five culturally tailored dietary profiles were designed according to international diabetes guidelines and adjusted to traditional food habits. Data were collected with two different semi-structured questionnaires. Changes in food consumption were assessed through McNemar's test, while paired Wilcoxon Signed-Rank test was used to analyze pre and post intervention. Fifty-five patients were enrolled. At follow-up, cereals, meat, and potatoes intake significantly improved, and the number of adequate dietary habits for each patient increased significantly. Transcultural mediator support was 90% positively evaluated. Adherence to dietary control is favorably influenced by a transcultural intervention, which is based on clinical and socio-cultural criteria, in compliance with patient's lifestyles.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta/métodos , Autogestão , Adulto , África do Norte/etnologia , Idoso , Bangladesh/etnologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
PLoS One ; 15(10): e0240831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064748

RESUMO

INTRODUCTION: Chagas Disease (CD) is endemic in many Latin-American countries, Bolivia in particular. It is now spreading in Italy as a host country for transcontinental migrants and becoming an emerging health problem. This anthropological action-research, as part of a wider medical project on Neglected Tropical Diseases, has the purpose of analyzing the sociocultural construction of CD and its representation in Bolivian people living in Rome as well as barriers, such as the stigma about the illness, to access the National Health Service for those potentially affected. METHODS: The ethnographic study was carried out from 2016 to 2018 by a medical anthropologist at the National Institute for Health, Migration and Poverty (INMP) on 72 Bolivian migrants (47 women and 25 men) living in Rome. The study was carried out through: a territorial mapping of Bolivian networks and communities aimed at recruiting people, participant observation, and application of semi-structured and unstructured interviews. The interviews were hold in Spanish and proposed to all participants before or during medical examination, or during events organized by the Bolivian community in Rome. The interview consisted of 16 items and covered four macro areas: personal and migration history, health status, access to the Italian National Health Service and knowledge about CD; plus 5 items for those who received a diagnosis of Chagas Disease in Italy. RESULTS: The sociocultural construction and the deep stigma about the illness built by participants and their families could hinder both diagnosis and treatment. Institutional barriers also contributed to reduce adherence to screening tests: often, opening hours of the outpatient clinic were incompatible with participants' precarious employments. To guarantee participant's access to public health services and their adherence to the diagnostic protocol, we implemented a profound revision of our cultural and institutional approach to them. CONCLUSIONS: The analysis evidenced the limitations of the conventional approach applied by the Italian National Health Service to this migrant community, such as the absence of socio-cultural and linguistics competences that can help understanding patients' perception and representation of the illness. The multidisciplinary approach instead-with clinicians using the ethnographic results to adjust their work to the participants' needs-was a successful attempt to ensure therapeutic alliance.


Assuntos
Doença de Chagas/patologia , Acesso aos Serviços de Saúde , Estigma Social , Migrantes/psicologia , Adolescente , Adulto , Bolívia , Doença de Chagas/epidemiologia , Barreiras de Comunicação , Carência Cultural , Feminino , Humanos , Entrevistas como Assunto , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pobreza , Adulto Jovem
10.
Int J Infect Dis ; 101: 126-130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32947054

RESUMO

OBJECTIVE: This study aimed to address the prevalence of infectious diseases in a population of unaccompanied immigrant minors living in reception centres of Rome, Italy. METHODS: The study was carried out from January 2013 to January 2019. All unaccompanied immigrant minors were screened for hepatitis B, hepatitis C, syphilis and latent tuberculosis infection. RESULTS: A total of 879 unaccompanied immigrant minors, 858 males and 21 females, aged 13-18 years old were studied. Of these, 615 were from Africa, 179 from Asia and 84 from Eastern Europe. A low prevalence of HBsAg carriage (2.5%) was observed as was very low prevalence of hepatitis C (0.72%) and latent syphilis (0.4%); latent tuberculosis, defined as tuberculin skin test (TST)+ X-ray case, was diagnosed in 102 (12%) minors. CONCLUSIONS: Similar to previous studies, these data demonstrate that migrant minors are generally healthy. However, given the relatively high prevalence of hepatitis B and latent tuberculosis, systematic screening for these diseases among immigrant minors immigrants is highly recommended for early detection and treatment of potentially transmissible diseases.


Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Tuberculose Latente/epidemiologia , Sífilis/epidemiologia , Migrantes/estatística & dados numéricos , Adolescente , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Humanos , Tuberculose Latente/diagnóstico , Masculino , Programas de Rastreamento , Menores de Idade/estatística & dados numéricos , Prevalência , Saúde Pública , Cidade de Roma/epidemiologia , Sífilis/diagnóstico , Teste Tuberculínico , Adulto Jovem
11.
PLoS One ; 15(4): e0222969, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352958

RESUMO

In inflammatory skin conditions, such as psoriasis, vascular enlargement is associated with endothelial cell proliferation, release of cytokines and adhesion molecule expression. Interleukin (IL)-17A is a pro-inflammatory cytokine mainly secreted by T helper-17 cells that is critically involved in psoriasis pathogenesis. IL-36α, IL-36ß and IL-36γ are also inflammatory cytokines up-regulated in psoriasis and induced by various stimuli, including IL-17A. In this study, we found that human keratinocytes are the main source of IL-36, in particular of IL-36γ. This cytokine was strongly induced by IL-17A and, together with IL-17A, efficiently activated human dermal microvascular endothelial cells (HDMECs), which expressed both IL-17 and IL-36 receptors. Both IL-36γ and IL-17A induced cell proliferation through specific molecular cascades involving ERK1/2 only or ERK1/2, STAT3 and NF-κB, respectively. We highlighted the intense IL-17A- and IL-36γ -dependent interplay between keratinocytes and HDMECs, likely active in the psoriatic lesions and leading to the establishment of a cytokine network responsible for the development and maintenance of the inflamed state. IL-17A or IL-36γ showed in HDMECs a synergic activity with TNF-α by potently inducing inflammatory cytokine/chemokine release and ICAM-1 expression. We also investigated the involvement of IL-36γ and VEGF-A, substantially reduced in lesional skin of psoriatic patients pharmacologically treated with the anti-IL-17A antibody Secukinumab. Importantly, keratinocyte-derived IL-36γ represented an additional pro-angiogenic mediator of IL-17A. We observed that keratinocyte-derived VEGF-A influenced proliferation but did not act on expression of adhesion molecules in HDMECs. On the other hand, inhibition of IL-36γ released by IL-17A-treated keratinocytes impaired either proliferation or ICAM-1 expression both in HDMECs and in an in vivo murine model of psoriasis. Taken together, our data demonstrated that IL-17A and IL-36γ are highly involved in endothelial cells/keratinocytes crosstalk in inflammatory skin conditions.


Assuntos
Comunicação Celular , Células Endoteliais/metabolismo , Interleucina-17/metabolismo , Interleucina-1/metabolismo , Queratinócitos/metabolismo , Psoríase/metabolismo , Células Cultivadas , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Eur J Dermatol ; 30(1): 3-11, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32250253

RESUMO

BACKGROUND: Platelet lysate (PL) contains a cocktail of growth factors and cytokines that promote tissue repair and regeneration. In vitro studies have shown that PL may affect the reparative function of keratinocytes and fibroblasts, but little is known about the effect of PL on immune cells involved in wound healing. OBJECTIVES: To analyse the effects of PL on T cells involved in the wound repair process. MATERIALS AND METHODS: The effect of PL on T cell proliferation, activation, and cytokine production was measured by ELISA and cytofluorometry and regulatory function based on cytofluorometry and Foxp3 RNA expression. Using an in vitro model of wound healing, we investigated the effect of PL-treated T cells on fibroblast proliferation and production of fibronectin and type-1 collagen as well as keratinocyte migration. RESULTS: PL induced T lymphocyte proliferation and CD69 expression, and promoted a transient upregulation of IFN-γ and TNF-α. However, later on, PL enhanced the number of CD25+ T cells releasing TGF-ß and expressing Foxp3 RNA, which was accompanied by a suppression in the level of type 1 cytokines. In the in vitro model, supernatants of PL-treated T cells positively affected the reparative capacity of human keratinocytes and induced fibroblast proliferation and production of fibronectin and type-1 collagen. CONCLUSION: These results indicate that PL temporally regulates T cells during the healing process, enhancing protective cytokines in the early phase, followed by a prominent expansion of TGF-ß+ T regulatory cells that promote tissue regeneration and dampen the inflammatory response to prevent excessive tissue damage.


Assuntos
Plaquetas , Fibroblastos/metabolismo , Queratinócitos/fisiologia , RNA/metabolismo , Linfócitos T Reguladores/metabolismo , Cicatrização , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/biossíntese , Fibronectinas/biossíntese , Fatores de Transcrição Forkhead/genética , Humanos , Técnicas In Vitro , Interferon gama/biossíntese , Lectinas Tipo C/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T Reguladores/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Regulação para Cima
13.
J Pathol Clin Res ; 6(1): 55-68, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577850

RESUMO

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-ß and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-ß were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.


Assuntos
Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Erupção por Droga/imunologia , Hidradenite Supurativa/tratamento farmacológico , Psoríase/induzido quimicamente , Adulto , Erupção por Droga/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/genética , Psoríase/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
J Immigr Minor Health ; 22(2): 426-431, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31399903

RESUMO

In many contexts, individuals with lower socioeconomic status, especially immigrants, have a higher burden of negative alcohol-related consequences and a higher probability of receiving a psychiatric diagnosis. This study aimed at exploring sociodemographic and clinical characteristics associated with harmful use of alcohol (HUA) among immigrant patients. A cross-sectional study was conducted in Rome (Italy) on a sample of 330 immigrant patients admitted to the gastroenterology outpatient clinic of the INMP (March 2013-October 2014). HUA was evaluated through the Alcohol Use Disorders Identification Test (AUDIT) questionnaire. The presence of psychiatric disorders was diagnosed through SCID I-II interviews. The association between sociodemographic characteristics and psychiatric disorders and HUA was evaluated through a multivariate log-binomial regression model. HUA was associated with unemployment, longer stay in Italy, mood disorder and not being married, especially among African immigrants. We provide original findings about a selected, hard-to-investigate population, suggesting priorities in interventions on HUA among specific vulnerable subgroups.


Assuntos
Alcoolismo/etnologia , Emigrantes e Imigrantes/psicologia , Pacientes/psicologia , Populações Vulneráveis , Adulto , África/etnologia , Estudos Transversais , Europa Oriental/etnologia , Feminino , Humanos , Itália , Masculino , Transtornos Mentais , Pessoa de Meia-Idade , Classe Social
15.
Cell Death Dis ; 9(11): 1104, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30377293

RESUMO

IL-36 cytokines, a subgroup of IL-1 family, comprise IL-36α, IL-36ß, and IL-36γ agonists, abundantly expressed in psoriatic skin, and IL-36RA and IL-38 antagonists. In psoriatic skin, IL-36 cytokines interfere with keratinocyte cornification programs and induce the release of antimicrobial peptides and chemokines active on neutrophils and Th17 lymphocytes. To date, the role of IL-38 antagonist in psoriasis remains to be defined. Here, we demonstrate that skin and circulating IL-38 levels are reduced in psoriatic patients and in other skin diseases characterized by neutrophilic infiltrate. In psoriasis, the balance of IL-36γ agonist/IL-38 antagonist serum levels is in favor of agonists and is closely associated with disease severity. Interestingly, IL-38 is upregulated by anti-IL-17A biological treatment and positively correlates with the therapeutic efficacy of secukinumab in psoriatic patients. The downregulation of IL-38 expression is strictly related to keratinocyte de-differentiation triggered by the inflammatory cytokines IL-36γ, IL-17, and IL-22. Finally, we demonstrate that administration of recombinant full-length IL-38 counteracts in vitro the biological processes induced by IL-36γ in human keratinocytes and endothelial cells and attenuates in vivo the severity of the psoriasiform phenotype induced by IMQ in mice. Such effects are achieved by restoring the physiological programs of keratinocyte proliferation and differentiation, and reducing the immune cell infiltrates.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Fatores Imunológicos/farmacologia , Interleucina-17/genética , Interleucinas/genética , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Imiquimode/administração & dosagem , Interleucina-1/genética , Interleucina-1/imunologia , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Interleucinas/imunologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Cultura Primária de Células , Psoríase/genética , Psoríase/imunologia , Psoríase/patologia , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia
16.
Eur J Dermatol ; 28(4): 457-466, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30129532

RESUMO

BACKGROUND: Eosin has been traditionally employed as a topical treatment for psoriasis, but the biological mechanism of its therapeutic action has not been fully elucidated. OBJECTIVES: To analyse eosin effects on psoriatic skin in vivo and keratinocytes and endothelial cells in vitro. MATERIALS & METHODS: Skin biopsies were taken from psoriatic plaques before and after a three-day eosin treatment and processed for histological analysis. Cultured human psoriatic keratinocytes and dermal endothelial cells were treated with eosin, and release of inflammatory chemokines was analysed by multiplexed bead-based immunoassay and ELISA. RESULTS: In patients, the three-day eosin treatment significantly reduced the number of infiltrating T lymphocytes, neutrophilic granulocytes, and dermal dendritic cells. A reduction in VEGF-A expression was also observed. In vitro, eosin treatment significantly decreased the release of CCL2, CCL5, and VEGF-A by keratinocytes and angiopoietin-2 by endothelial cells. CONCLUSIONS: Eosin treatment impacts on psoriatic inflammatory infiltrates and dampens the release of proinflammatory chemokines and angiogenic factors.


Assuntos
Fármacos Dermatológicos/farmacologia , Amarelo de Eosina-(YS)/farmacologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Angiopoietina-2/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/imunologia , Fármacos Dermatológicos/uso terapêutico , Células Endoteliais/fisiologia , Amarelo de Eosina-(YS)/uso terapêutico , Humanos , Queratinócitos/fisiologia , Infiltração de Neutrófilos , Psoríase/metabolismo , Psoríase/patologia , Linfócitos T/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
J Exp Med ; 214(5): 1529-1546, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28428203

RESUMO

T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.


Assuntos
Citocinas/fisiologia , Células Dendríticas/fisiologia , Ligante OX40/fisiologia , Células Th2/fisiologia , Diferenciação Celular/fisiologia , Quimiocina CXCL13/metabolismo , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucinas/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Receptores CXCR5/metabolismo , Receptores Imunológicos/metabolismo
20.
Eur J Immunol ; 47(4): 607-614, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28295238

RESUMO

IL-17 and IL-22 are tissue-signaling cytokines that favor protection and regeneration of barrier organs such as the skin, lung, and gastrointestinal system. Both cytokines share cellular sources, signaling pathways, and functional aspects; however, taking a closer look they differ, e.g. in their pro-inflammatory or regenerative potential. An imbalance of the carefully orchestrated tissue-signaling system might result in autoimmune diseases, promote cancer growth, or predispose to infectious diseases. This review highlights recent understandings in cellular sources, signaling mechanisms, physiologic as well as pathogenic role of the double-faceted cytokines IL-17 and IL-22.


Assuntos
Imunidade , Infecções/imunologia , Interleucina-17/imunologia , Interleucinas/imunologia , Intestinos/imunologia , Pulmão/imunologia , Neoplasias/imunologia , Pele/imunologia , Células Th17/imunologia , Animais , Autoimunidade , Humanos , Regeneração , Transdução de Sinais
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