RORγt⁺ T_reg cells

Microbiota imbalances or depletion in early life can lead to greater susceptibility to allergy. In Science, Eberl and colleagues show that the microbiota balances type 2 responses through the local induction of T_reg cells that express the transcription factor RORγt. These IL-17⁻IL-10⁺Foxp3⁺RORγt⁺T_reg cells are induced by oral antigen– and microbiota-derived short-chain fatty acids and are lost in germ-free or antibiotic-treated mice. Similar to T_H17 cells, they are induced by segmented filamentous bacteria and are dependent on IL-6 and IL-23, and similar to T_reg cells, they are dependent on retinoic acid. Mice with Foxp3-driven deletion of RORγt show greater susceptibility to type 2 response–mediated colitis and are more resistant to helminth infection, whereas they have normal T_H1 or T_H17 responses. Thus, microbiota-induced type 3 RORγt⁺ T_reg cells and T_H17 cells regulate type 2 immunity, possibly through expression of the immunomodulatory receptor CTLA-4 by RORγt⁺ T_reg cells and activation of DCs.

Science (9 July 2015) doi:10.1126/science.aac4263