Lineage Relationship Analysis of RORγt+ Innate Lymphoid Cells

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Science  29 Oct 2010:
Vol. 330, Issue 6004, pp. 665-669
DOI: 10.1126/science.1194597

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Innate Innit?

Innate lymphocytes (ILCs) are a recently described population of immune cells that produce cytokines like those associated with T helper cells, but lack the recombined antigen receptors characteristic of T cells. Again, like some T helper cell lineages, a proportion of ILCs express the transcription factor RORγt. These include lymphoid tissue inducer (LTi) cells required for fetal lymphoid tissue organogenesis and a population of natural killer (NK)–like cells that function in gut immune responses. Sawa et al. (p. 665; see the Perspective by Veldhoen and Withers) wondered whether the RORγt-expressing ILCs all develop from the same progenitor population. Indeed, they found a fetal liver progenitor that gave rise to several phenotypically distinct populations. However, the LTi cells were not progenitors for the NK-like cells. It seems the trajectory of different ILC populations is developmentally regulated, and postnatally ILCs are favored that play a role in intestinal defense before the gut is fully colonized by intestinal microbiota.


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.

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