Aryl hydrocarbon receptor expressing Treg17 cells suppress type 1 diabetes in NOD mice (BA11P.140)

Abstract

Abstract The role of Th17 cells in type 1 diabetes (T1D) remains inconclusive. We found polarizing CD4+ T cells with TGF-beta+IL-6 or with IL-23+IL-6 cytokines induces different subsets of Th17 cells. Cells polarized with TGF-beta+IL-6 express high levels of transcription factor aryl hydrocarbon receptor (AhR) and IL-10 but minimal amounts of IL-22. Cells from T cell receptor transgenic BDC2.5 NOD mice polarized with IL-23+IL-6 produced large amounts of IL-22, expressed little AhR expression but induce T1D in young NOD mice. Cells derived with TGF-beta+IL-6 and termed as Treg17 cells were nonpathogenic and did not induce T1D. All adoptive transfer studies were done in young NOD mice and not NOD.SCID mice to prevent the conversion of Th17 cells into Th1 cells. We have also found IL-22-producing Th17 cells in the pancreas of diabetic NOD mice. The expression of IL-22 receptor in the pancreas of NOD mice increased with disease progression. Neutralization of IL-22 by antibody in vivo during adoptive transfer of pathogenic Th17 cells or splenocytes from diabetic mice did not significantly alter disease progression in the recipient mice. Therefore, Th17 derived IL-22 is not directly pathogenic to beta cells. We conclude regulatory Treg17 cells induced by TGF-beta+IL-6 that express high levels of AhR are protective while Th17 cells with a very low level of AhR induced by IL-23 + IL-6 are pathogenic. Both EN and SMB equally contributed to this work.