Escaping Negative Selection: ILC You in the Gut

Abstract

How commensal-specific T cells are controlled in the periphery is poorly understood. In a recent issue of Science, Hepworth et al. (2015) show that ILC3s induce apoptosis of microbiota-specific CD4 T cells in a form of extrathymic negative selection.

Figure 1. Selection of Self-Reactive and Commensal-Specific CD4 T Cells

(Left) In the thymus, bone marrow-derived APCs, such as DCs, and mTECs eliminate self-reactive CD4 T cells either through the induction of apoptosis during negative selection or re-direction to the Treg cell lineage. (Right) In the MLN, activated commensal-specific CD4 T cells are either directed to the Treg cell lineage by CD103⁺ DCs or deleted through induction of apoptosis by MHCII⁺ ILC3s in a process of “intestinal selection.” ILC3s induce apoptosis by IL-2 withdrawal, which activates Nur77 and the proapoptotic factor Bim. Conditional deletion of MHCII on ILC3 (MHCII^ΔILC3 mice) prevents deletion and leads to expansion of commensal-specific CD4 T cells, which results in intestinal inflammation in the presence of appropriate microbiota.