Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity

Type 1, 2, and 3 innate lymphoid cells (ILCs) have emerged as tissue-resident innate correlates of T helper 1 (Th1), Th2, and Th17 cells. Recent studies suggest that ILCs are more diverse than originally proposed; this might reflect truly distinct lineages or adaptation of ILCs to disparate tissue microenvironments, known as plasticity. Given that ILCs strikingly resemble T cells, are they redundant? While the regulation, timing, and magnitude of ILC and primary T cell responses differ, tissue-resident memory T cells may render ILCs redundant during secondary responses. The unique impact of ILCs in immunity is probably embodied in the extensive array of surface and intracellular receptors that endow these cells with the ability to distinguish between normal and pathogenic components, interact with other cells, and calibrate their cytokine secretion accordingly. Here I review recent advances in elucidating the diversity of ILCs and discuss their unique and redundant functions. Innate lymphoid cells (ILCs) are tissue-resident correlates of T helper 1 (Th1), Th2, and Th17 cells. Colonna reviews recent advances in understanding ILC diversity and functional plasticity—their unique and redundant functions, receptor repertoires, and regulation of gene-expression programs.