Lineage Relationship Analysis of RORγt + Innate Lymphoid Cells

Abstract

Lymphoid tissue–inducer (LTi) cells initiate the development of lymphoid tissues through the activation of local stromal cells in a process similar to inflammation. LTi cells express the nuclear hormone receptor RORγt, which also directs the expression of the proinflammatory cytokine interleukin-17 in T cells. We show here that LTi cells are part of a larger family of proinflammatory RORγt⁺ innate lymphoid cells (ILCs) that differentiate from distinct fetal liver RORγt⁺ precursors. The fate of RORγt⁺ ILCs is determined by mouse age, and after birth, favors the generation of cells involved in intestinal homeostasis and defense. Contrary to RORγt⁺ T cells, however, RORγt⁺ ILCs develop in the absence of microbiota. Our study indicates that RORγt⁺ ILCs evolve to preempt intestinal colonization by microbial symbionts.