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

Abstract

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-like B cell subsets during immune responses: Beyond antibody production

“…In addition to typically recognized innate cells such as Mϕs or polymorphonuclear leukocytes, the innate lymphocytes that include the well documented NK cells that have been recently included into the family of the so‐called ILCs constitute the cellular arm of the innate immune system …”

“…The innate‐like attribute of NKBs, beyond the convergent phenotypes of both NK and B cells and their repertoire limitations, comes from their efficient ability to secrete IL‐18 and IL‐12 upon microbial infections . These cytokines can rapidly activate NK cells and ILC1s, thus playing a pivotal role in innate immune responses against infectious agents (mainly intracellular pathogens) by priming group 1 ILCs …”

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

“…4,5 In addition to Th17 cells, several other cell types are described as sources for IL-17, including CD8 + T cells, 6,7 γδ T cells 8,9 and innate lymphoid cells. 10 The presence of IL-17 and IL-17-expressing cells has recently been studied in several types of cancer, including NSCLC. [11][12][13][14][15][16] High serum IL-17 levels were detected in NSCLC patients and were significantly correlated with a late stage of NSCLC, overall survival (OS), and disease-free survival (DFS).…”

Thinking differently about ILCs—Not just tissue resident and not just the same as CD4+ T‐cell effectors

“…The field now recognizes the important roles of yet another set of lymphocytes that contribute to host defense during this critical time window but lack the rearranging, clonally distinct receptors that characterize αβ and γδ T cells, namely innate lymphocytes or ILCs. ILCs emerge from common lymphoid progenitors (CLPs) and are functionally diverse, with an array of effector phenotypes that resembles that of polarized T‐cell subsets . Conventional natural killer (cNK) cells are prototypic members of the ILC family that were described decades ago and possess effector functions similar to those of CD8 + cytotoxic T cells.…”