DIM mitigates the development of experimental autoimmune encephalomyelitis by maintaining the stability and suppressive function of regulatory T cells

•Tregs proliferated but failed to prevent the autoimmune responses in EAE model.•DIM maintained the stability and suppressive function of Tregs in EAE model.•DIM alleviated the severity of EAE model not by facilitating Treg differentiation.•The influence of DIM on the activities of Tregs was in an AhR dependent manner. Recent studies have revealed that indoles, dietary ligands of the aryl hydrocarbon receptor (AhR), have immunomodulatory characteristics of balancing the differentiation of regulatory T cells (Tregs) and Th17 cells in multiple autoimmune diseases. In this study, we aimed to investigate the potency of the indole, 3,3′-diindolylmethane (DIM), on the stability and suppressive function of Tregs in experimental autoimmune encephalomyelitis (EAE). Furthermore, we used the AhR antagonist CH223191 to verify that DIM exerts its effects on Tregs through the activation of AhR. We found that DIM treatment significantly alleviated the severity of EAE by maintaining the stability and suppressive function of Tregs instead of facilitating the differentiation of Tregs. Thus, these DIM-treated Tregs might indirectly inhibit the generation of Th17 cells and the production of proinflammatory cytokines. And we confirmed the critical role of AhR in the EAE model. Our study further investigated the mechanisms by which dietary indoles promote Treg activity in the EAE model. DIM may act as a novel therapeutic to restrain autoimmune inflammation in multiple sclerosis.