An embarrassment of riches: RORγt+ antigen-presenting cells in peripheral tolerance

Abstract

RORγt⁺ regulatory T (Treg) cells are critical toward maintaining gut immune tolerance. In recent studies published in Nature, Kedmi et al., Lyu et al., and Akagbosu et al. describe MHCII⁺RORγt⁺ antigen-presenting cells that mediate RORγt⁺ Treg cell differentiation but propose disparate identities for these cells.

Fig. 1:. Regulation of Intestinal tolerance by RORγt⁺ APCs:

Akagbosu et al demonstrated that Thetis Cells (TC) present commensal antigens and in concert process active TGFβ1 through αVβ8 integrin to induce the differentiation of RORγt⁺ Treg cells early in life. RORγt⁺ Treg cells stably persist through adult life and promote tolerance by suppressing inflammatory response to the microbiota. Kedmi et al and Lyu et al showed that commensal antigens are processed by RORγt⁺ ILC3s (and for Kedimi et al possibly JCs as well) to induce RORγt⁺ Treg cells also by aTGFβ1-αVβ3/8 integrin dependent mechanism. ILC3-dependent tolerance may become prominent with age to suppress inflammatory responses to colitogenic commensals. The schematics were prepared using BioRender.