AIM2 promotes T_H17 cells differentiation by regulating RORt transcription activity

AIM2 is an interferon-inducible HIN-200 protein family member and is well-documented for its roles in innate immune responses as a DNA sensor. Recent studies have highlighted AIM2's function on regulatory T cells (Treg) and follicular T cells (Tfh). However, its involvement in Th17 cell differentiation remains unclear. This study reveals that AIM2 promotes Th17 cell differentiation. AIM2 deficiency decreases IL-17A production and downregulates key Th17 associated proteins (ROR gamma t, IL-1R1, IL-23R). AIM2 is located in the nucleus of Th17 cells, where it interacts with ROR gamma t, enhancing its binding to the Il17a promoter. The absence of AIM2 hinders naive CD4 T cells from differentiating into functional Th17 cells and from inducing colitis in Rag1(-/-) mice. This study uncovers AIM2's role as a regulator of Th17 cell transcriptional programming, highlighting its potential as a therapeutic target for Th17 cell-mediated inflammatory diseases.