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BMC Immunol ; 18(1): 8, 2017 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-28166724

RESUMO

BACKGROUND: Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion. However, it is unknown whether and how IL-17 mediates synovial IgA production. Here we aim to investigate the connection of synovial IL-17 with IgA production in the joint. In this study we included synovial fluids (SF) from patients with rheumatoid arthritis (RA; n = 66), spondyloarthritis (SpA; n = 18) and osteoarthritis (OA; n = 36). The levels of IL-17, IL-6, transforming growth factor (TGF)-ß1, B-cell-activating factor of the TNF family (BAFF) and anti-lipopolyssacharide (LPS) immunoglobulin (Ig)A were investigated by enzyme-linked immunosorbent assay (ELISA). Total IgA was measured by radial immunodiffusion assay. Synovial fluid-derived mononuclear cells (SFMC) were stimulated with bacterial antigens or SF-conditioned media, and cytokines and IgA were analyzed in the supernatants. RESULTS: IL-17, IL-6 and TGF-ß1 were increased in SF from both RA and SpA compared with OA patients. Concentration of IL-17 correlated with the disease activity score (DAS)-28, IL-6 and anti-LPS IgA levels. Bacterial-stimulated SFMCs from RA and SpA patients secreted higher IL-17 than vehicle-stimulated SFMCs. Conditioned media with SF containing IL-17 induced anti-LPS IgA production by SFMCs which was independent of IL-6 activity. Concentrations of synovial TGF-ß1 and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF-ß1 and anti-LPS IgA by SF-stimulated SFMCs. CONCLUSIONS: This study reports a connection between IL-17 and IgA secretion in the joint. In addition, it demonstrates that enterobacterial antigens trigger synovial IL-17 production, and that TGF-ß1 and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.


Assuntos
Infecções por Enterobacteriaceae/imunologia , Inflamação/imunologia , Interleucina-17/metabolismo , Mucosa Intestinal/imunologia , Articulações/imunologia , Espondilite Anquilosante/imunologia , Células Th17/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fator Ativador de Células B/metabolismo , Criança , Feminino , Humanos , Imunoglobulina A/metabolismo , Interleucina-17/imunologia , Mucosa Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Adulto Jovem
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