LAUSR

Graphical abstract Figure. No Caption available. HighlightsIL33 enhances Th17 cell differentiation through DC maturation.IL33 does not directly induce differentiation of naïve CD4+ T cells to Th17 cells.IL33‐matDCs increase surface molecule‐expressions driving T cell activation.IL33‐matDCs promote Th17 cell responses via DC‐derived IL‐1&bgr; 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 OVA323‐339 peptide, and their Th17 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&bgr; 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&ggr;t), but IL‐33 did not directly affect CD4+ T cell differentiation or increase Th17 polarization. Notably, neutralizing IL‐1&bgr; 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&bgr; and IL‐6 derived from IL‐33‐matured DCs.