The evolution of innate lymphoid cells

Abstract

Innate lymphoid cells (ILCs) are the most recently discovered group of immune cells. Understanding their biology poses many challenges. We discuss here the current knowledge on the appearance of ILC subsets during evolution and propose how the connection between ILCs and T cells contributes to the robustness of immunity and hence to the fitness of the hosts.

Figure 1

Differentiation and evolution of ILCs. Model of lymphoid cell phylogeny (left), extending from the putative common vertebrate ancestor to birds and mammals (dashed lines and question marks indicate uncertainties), with the putative presence of certain cell types in some cases based on transcriptomics (for example, orthologs), and a model of ILC-differentiation pathways based mainly on transcriptional-program analysis in the mouse (right)^,,; line colores based on data in Figure 3. ILC2p, ILC2 precursor; CLP, common lymphoid progenitor; CILP, common ILC precursor; NKP, NK-cell precursor; CHILP, common helper innate lymphoid precursor; Mya, million years ago.

Figure 2

Phylogeny of ILC signature genes. Analysis of genes ‘preferentially’ expressed by the various types of ILCs or their progenitors in mice, with an immunocyte-transcriptomic compendium built by merging of expression profiles available in the GEO genomics data repository, plus the inclusion of genes encoding products shown to be involved in ILC differentiation (for example, Id2, Nfil3, Gata3), followed by a search for orthologous genes in lampreys, bony fishes (actinopterygii; n = 10 species), amphibians (Xenopus; n = 1 species), reptiles (n = 2 species), birds (n = 5 species) and mammals (n = 41 species) by querying of the Biomart database from Ensembl (http://www.biomart.org/) and OrthoDB developed by the Zdobnov’s Computational Evolutionary Genomics group (http://cegg.unige.ch/). Numbers (and colors) in plot indicate frequency of a species in the family in which an orthologous gene has been identified.

Figure 3

Innate and adaptive lymphocytes exhibit both complementarity and redundancy in immunity. ILCs serve functions that are both distinct from and overlap those of adaptive immune cells; gut ILC3 cells serve as the example here. Intestinal T cells and ILC3 cells contribute to contain intestinal infections via their production of IL-22. The unique functions of ILC3 cells (bottom left) are based on published reports^,–. ILC3 cells can secrete the cytokines IL-17, IL-22, GM-CSF and lymphotoxins that contribute to protective immunity but also to inflammatory disorders via interaction with other cells, such as T cells^,, dendritic cells^, and neutrophils. Precise delineation of the selective roles of NCR⁻ ILC3 cells versus those of NCR⁺ ILC3 cells has not yet been reported, with the exception of the control of cecal homeostasis upon infection with C. rodentium and the promotion of inflammation in colitis induced by antibody to the costimulatory receptor CD40 (anti-CD40), which are properties of NCR⁺ ILC3 cells. RegIIIβ, anti-microbial peptide; T_FH cell, follicular helper T cell; DC, dendritic cell; IgA, immunoglobulin A; MHC, major histocompatibility complex; GvHD, graft-versus-host disease.