Development, Differentiation, and Diversity of Innate Lymphoid Cells

Abstract

Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILC). ILC are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILC has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILC can be grouped into two separate lineages, cytotoxic ILC represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILC (i.e., ILC1, ILC2, ILC3). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces.

Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network

“…The second group consists of genes that are normally not activated to substantial levels at all during the phase 1 stages. Curiously, these are highly enriched for genes used in NK cells, ILCs, and innate-like T cells, including the powerful regulatory genes Id2, Zbtb16, and Nfil3 (6,42,(49)(50)(51)(52)(53)(54)(55). Many of these genes, especially NK-associated genes, require continual Bcl11b action to keep them silent later (Fig.…”

Innate Lymphoid Cells in Graft-Versus-Host Disease

“…ILC3 express the transcription factor RORγt, and the development of mouse ILC3 depends on RORγt, Notch, and Tcf1, as recently summarized elsewhere 6. Additionally, the transcription factor aryl hydrocarbon receptor (Ahr) is crucial in the maintenance and function of ILC3 4.…”

“…Alike these latter cell types, ILC develop from the common lymphoid progenitor (CLP). However, in contrast to T and B cells, ILC critically depend on the transcriptional repressor Id2 for commitment to the ILC lineage 6. The Id2‐dependent ILC progenitor (ILCp) or common innate lymphoid progenitor (CLIP) gives rise to all ILC subsets including NK cells.…”

“…The Id2‐dependent ILC progenitor (ILCp) or common innate lymphoid progenitor (CLIP) gives rise to all ILC subsets including NK cells. Furthermore, as a progenitor of ILC1, ILC2, and ILC3, the common helper‐like innate lymphoid progenitor (CHILP) was identified, which depends on the transcription factors PLZF, GATA3, NFIL‐3, and Notch 6, 7. The development of human ILC and their progenitor(s) are less well characterized.…”

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…The innate lymphoid cell (ILC) family has been the focus of intense investigation over recent years and ILC have emerged as key players in immune responses within multiple organs, particularly barrier surfaces such as the lung, skin and gastrointestinal tract 1, 2, 3, 4. The current nomenclature broadly divides ILC into three subgroups that are defined by their master transcription factor usage and cytokine‐producing capacity, and which closely mirror CD4 + T helper (Th) cell subsets 3.…”