Cytokine-Mediated Regulation of Innate Lymphoid Cell Plasticity in Gut Mucosal Immunity

Abstract

Mucosal barriers are active sites that encounter a bombardment of antigenic stimuli derived from both the commensal flora and a variety of pathogens, as well as from environmental insults. As such, the ability to mount appropriate innate immune responses is an important first line of defense that confers protection to the host. Central to innate immunity are innate lymphoid cells (ILCs), which were first described a decade ago, and represent a family of heterogeneous cells driven by specific transcription factors and exhibit distinct cytokine profiles that are shared with their CD4+ T-helper cell counterparts. ILCs are particularly enriched at mucosal surfaces, and the tissue microenvironment and cytokine milieu in which ILCs reside are critical factors that drive the behavior and overall function of these cells. In fact, ILCs situated at mucosal barriers must be able to temper their response to a constant exposure of environmental antigens, but also promptly react to pathogens or signals that are potentially harmful to the host. In this context, the ability of ILCs to readily transdifferentiate in response to their dynamic surroundings has become a vigorous area of research, and defining specific mechanism(s) of ILC plasticity is at the advent of discovery. This review will summarize what is currently known regarding the network of cytokines and regulatory elements that enable ILCs to readily transform, based on the range of diverse signals and signal gradients they encounter that lead to either protective or pathogenic function(s), with focus on the gut mucosal immune system.

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

“…ILCs are innate immune cells that regulate mucosal immune response ( 24 ). ILCs are important effector cells in the innate immune system ( 25 ).…”

Heterogeneity of ILC2s in the Intestine; Homeostasis and Pathology

“…Removal of the aryl hydrogen receptor, a transcription factor for ILC3, activates intestinal ILC2s, whereas increased aryl hydrogen receptor expression suppresses ILC2 function and enhances ILC3 function ( 153 ). As ILC3-to-ILC1 conversion has been reported ( 19 , 154 ), ILC2s also demonstrate plasticity, resulting in ILC2 heterogeneity in the inflammatory gut.…”

Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development

“…Application of these technologies to developing ILLs in the face of infection will also be important to understand how lineage plasticity contributes to the protective or pathogenic functions of ILLs. Recent studies have demonstrated plasticity between ILC3s and ILC2s with ILC1s, as well as between ILC3s with ILC2s, but whether this is a feature of all ILLs, or even adaptive lymphocytes, requires more investigation (133). Activation of iNKT1 cells allows these cells to access the iNKTfh cell program, suggesting that at least some degree of plasticity exists in innate-like T cells (57).…”