IL-33 changes CD25 hi Tregs to Th17 cells through a dendritic cell-mediated pathway.

Interleukin (IL)-33 is an alarmin factor that is highly secreted in a variety of autoimmune diseases, induces maturation of dendritic cells (DCs) and differentiation of T helper 17 (Th17) cells. As the balance between Th17 cells and regulatory T cells (Tregs) is important to maintain immune homeostasis, in this study, we investigated the effects of IL-33 on Treg cell response. We observed that direct treatment with IL-33 had no effect on Treg differentiation, whereas IL-33-matured DCs (IL33-matDCs) inhibited the differentiation of CD4 ⁺ T cells to Tregs by decreasing the expression of Foxp3. Furthermore, co-culture with IL-33-matDCs changed stable Tregs (CD25 ^hi CD4 ⁺ Tregs) to IL-17-producing cells, whereas IL-33-matDCs had little effects on unstable Tregs (CD25 ^lo CD4 ⁺ Tregs). The stable Tregs were demonstrated to express high levels of IL-6 receptors. Blocking of IL-6 secreted from IL-33-matDCs suppressed the conversion of Tregs to Th17 cells, indicating the greater propensity to convert stable Tregs to Th17 cells is due to IL-6 signaling. Taken together, these results demonstrate that IL-33 inhibits Treg differentiation and the conversion of stable Tregs to Th17 cells via DCs.
Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest regarding the publication of this paper.
(Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)