Innate Lymphoid Cells (Non‐NK ILCs)

Abstract

Until a decade ago, natural killer (NK) cells constituted the major-if not the soleplayer of innate lymphoid cell populations. The discovery of the presence and execution of curial functions by lymphoid tissue inducer-like cells (LTi) in adults is followed by the discovery of Th2-like innate cells and later Th1-like helper group 1 ILCs. With these findings, the innate lymphocyte family has expanded and a new paradigm has emerged. Apparently, innate versions of helper subsets of CD4+ T cells existed in humans and mice. These cells, unlike their adaptive counterparts, lack CD3, T and B cell receptors, do not rearrange their antigen receptors and get activated by microbial products or cytokines. Furthermore, these cells rely on similar transcription factors that helper CD4+ T cells use for their development and functions (such as T-bet, Gata3 and Rorγt); they produce similar effector cytokines (such as IFN-γ; IL-5, IL-13, IL-4; IL-17A, IL-22, GMCSF, respectively). Moreover, these cells assume crucial functions as an immediate, first line source of cytokines/chemokines against pathogens during protective immune responses. Lastly, very much like their adaptive counterparts, they are present and contribute to pathogenesis in various chronic inflammatory diseases of mice and humans in several tissues.

Fingolimod Alters Tissue Distribution and Cytokine Production of Human and Murine Innate Lymphoid Cells

“…More importantly, ILC3 involvement in the chronic inflammatory diseases such as Crohn's and colitis have been established in murine models as either pathogenic or protective agents in our and others' works (33–41). Increased ILC3 cellular presence or activity have been reported in the affected tissues or circulation in several other autoimmune disease patients from rheumatoid arthritis, psoriasis to MS warranting further study of these cells in human pathologies (42, 43). Although a population of ILC3s express NKp46 in mice and NKp44 in humans, it is completely unknown how S1P receptors regulate human or murine ILC3 biology or how drugs against S1P receptors would impact a critical mucosal innate cell population.…”

The role of innate lymphoid cells in selected disease states – cancer formation, metabolic disorder and inflammation

“…NK cells exhibit cytotoxic capabilities similar to CD8 + T cells [ 41 ], whereas ILC1 cells, by restricted cytotoxicity, are more closely related to Th1 (T helper) cells, which can activate mononuclear (MN) and polymorphonuclear (PMN) cells by increasing their capacities for cytotoxicity, phagocytosis, and neutrophil extracellular trap (NET) formation [ 38 , 39 , 42 ]. Group 1 ILCs include NK cells with phenotype CD3 – CD94 + CD56 + cells [ 43 ] and ILC1 cells which are Lin – CD127 + c-kit – CRTH2 – [ 44 ]. Simoni et al .…”

“…ILC-2 cells exhibit a protective effect of innate immune response against parasites, but they can also control cell metabolism, and participate in allergic reactions and wound healing [ 47 – 60 ]. In mice, ILC-2 cells are typically identified by flow cytometry and the expression of CD25, KLRG1, ICOS, or ST2 (subunits of the IL-33 receptor complex), but in humans by CD161, ST2, CRTH2 expression [ 49 ], or by Lin – CD127 + c-kit + CRTH2 + NCR – phenotype [ 44 ]. For ILC subsets, Simoni et al .…”

“…All cells of this group participate in immunological resistance against bacterial and fungal infections and participate in the development and repair of lymphoid tissue [ 68 – 77 ]. The flow cytometry analyses of the ILC-3 group include Lin - CD127 + c-kit + CRTH2 – NKp46 + /NKp44 + marker expression [ 44 ]. Hazenberg Spits [ 32 ] demonstrated that a clear definition of ILC-2 and ILC-3 populations in humans by multi-color flow cytometry requires at least eight fluorescence channels.…”