RESUMO
Although allergic contact dermatitis (ACD) is the most common T cell-mediated inflammatory responses against an allergen in the skin, the pathogenesis of ACD remains incompletely understood. In the sensitization phase in ACD, hapten-bearing dermal dendritic cells (DCs) play a pivotal role in the transport of an antigen to the lymph nodes (LNs), where they present the antigen to naïve T cells. Here we report that Allergin-1, an inhibitory immunoreceptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region, is highly expressed on dermal DCs. Mice deficient in Allergin-1 exhibited exacerbated fluorescein isothiocyanate (FITC)-induced type 2 contact hypersensitivity (CHS) such as ear swelling and skin eosinophilia. Allergin-1-deficient mice also showed larger numbers of CD4+ T cells and FITC-bearing DCs and greater expressions of type 2 cytokines, including IL-5, IL-10 and IL-13, in the draining LNs than did wild type mice. In sharp contrast, Allergin-1-deficient mice showed comparable level of type 1 CHS induced by 2,4-dinitrofluorobenzene (DNFB). These results suggest that Allergin-1 on dermal DC inhibits type 2, but not type 1, immune responses in the sensitization phase of CHS.
Assuntos
Células Dendríticas/metabolismo , Dermatite de Contato/metabolismo , Fluoresceína-5-Isotiocianato/química , Receptores Imunológicos/fisiologia , Pele/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Células Dendríticas/citologia , Dinitrofluorbenzeno/química , Feminino , Hipersensibilidade Imediata , Interleucina-10/biossíntese , Interleucina-13/biossíntese , Interleucina-5/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Receptores Imunológicos/metabolismoRESUMO
House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1-deficient CD11b+ bone marrow-derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.
Assuntos
Asma/imunologia , Hipersensibilidade/imunologia , Pneumonia/imunologia , Pyroglyphidae/imunologia , Receptores Imunológicos/imunologia , Animais , Células Dendríticas/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
INTRODUCTION: Elucidating the molecules involved in the inflammatory process of chronic Chagas disease may allow identification of treatment targets. METHODS: The ex vivo phenotypic expression of chemokine receptors CCR1, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4, and CXCR5 on the CD4+ and CD8+ T-cells of patients with chronic Chagas cardiomyopathy of varying severity was evaluated using flow cytometry. RESULTS: Differential expression of CD4+CCR3+ and CD8+CCR4+ T-cells was observed in patients with mild cardiac involvement compared, respectively, with patients with severe cardiac and asymptomatic forms of Chagas disease. CONCLUSIONS: These receptors are possibly involved in the pathogenesis of chronic Chagas cardiomyopathy.
Assuntos
Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/patologia , Receptores CCR/sangue , Idoso , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valores de Referência , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
Abstract INTRODUCTION: Elucidating the molecules involved in the inflammatory process of chronic Chagas disease may allow identification of treatment targets. METHODS: The ex vivo phenotypic expression of chemokine receptors CCR1, CCR3, CCR4, CCR5, CXCR2, CXCR3, CXCR4, and CXCR5 on the CD4+ and CD8+ T-cells of patients with chronic Chagas cardiomyopathy of varying severity was evaluated using flow cytometry. RESULTS: Differential expression of CD4+CCR3+ and CD8+CCR4+ T-cells was observed in patients with mild cardiac involvement compared, respectively, with patients with severe cardiac and asymptomatic forms of Chagas disease. CONCLUSIONS: These receptors are possibly involved in the pathogenesis of chronic Chagas cardiomyopathy.
