IL-33-matured dendritic cells promote Th17 cell responses via IL-1 beta and IL-6

Abstract

IL-33 is associated with a variety of autoimmune diseases, such as sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Although IL-33 is mainly involved in the induction of Th2 cells, however, the relationship between IL-33 and Th17 cells is still largely unknown. In this study, we investigated the effects of IL-33 on DC-mediated CD4(+) T cell activation and Th17 cell differentiation because DCs are essential cells for presenting self-antigens to CD4(+) T cells in autoimmune disease conditions. OT-II mice were injected with IL-33-treated DCs or untreated DCs that were primed by OVA(323-339 )peptide, and their Thl 7 cell responses were compared. Th17 cell population and IL-17 expression levels were significantly increased in draining lymph nodes of mice injected with IL-33-treated DCs, compared with those in mice injected with untreated DCs. IL-33 treatment maturated DCs to present self-antigens and to increase production of proinflammatory cytokines such as IL-1 beta and IL-6, which have a crucial role in Th17 cell differentiation. We found that the IL-33-matured DCs enhanced the expression of an early T cell activation marker (CD69) and the Th17 master transcription factor (ROR gamma t), but IL-33 did not directly affect CD4(+) T cell differentiation or increase Th17 polarization. Notably, neutralizing IL-1 beta and/or IL-6 significantly decreased IL-17 expression levels and Th17 cell population which were increased by the coculture of CD4(+) T cells with IL-33-matured DCs, indicating that IL-33 may induce Th17 cell responses via IL-1 beta and IL-6 derived from IL-33-matured DCs.