Control of the Development, Distribution, and Function of Innate-Like Lymphocytes and Innate Lymphoid Cells by the Tissue Microenvironment

Recently, considerable attention has been directed toward innate-like T cells (ITCs) and innate lymphoid cells (ILCs) owing to their indispensable contributions to immune responses, tissue homeostasis, and inflammation. Innate-like T cells include NKT cells, MAIT cells, and γδ T cells, whereas ILCs include NK cells, type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), and type 3 ILCs (ILC3s). Many of these ITCs and ILCs are distributed to specific tissues and remain tissue-resident, while others, such as NK cells and some γδ T cells, circulate through the bloodstream. Nevertheless, recent research has shed light on novel subsets of innate immune cells that exhibit characteristics intermediate between tissue-resident and circulating states under normal and pathological conditions. The local microenvironment frequently influences the development, distribution, and function of these innate immune cells. This review aims to consolidate the current knowledge on the functional heterogeneity of ITCs and ILCs, shaped by local environmental cues, with particular emphasis on IL-15, which governs the activities of the innate immune cells involved in type 1 immune responses.