Metabolic Regulation of Group 3 Innate Lymphoid Cells and Their Role in Inflammatory Bowel Disease.

Dongjuan Song,Zhihua Ran,Lijie Lai

doi:10.3389/fimmu.2020.580467

Dongjuan Song, Zhihua Ran + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2020.580467

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Abstract

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammatory disorder of the intestine. IBD is associated with complex pathogenesis, and considerable data suggest that innate lymphoid cells contribute to the development and progression of the condition. Group 3 innate lymphoid cells (ILC3s) not only play a protective role in maintaining intestinal homeostasis and gut barrier function, but also a pathogenic role in intestinal inflammation. ILC3s can sense environmental and host-derived signals and combine these cues to modulate cell expansion, migration and function, and transmit information to the broader immune system. Herein, we review current knowledge of how ILC3s can be regulated by dietary nutrients, microbiota and their metabolites, as well as other metabolites. In addition, we describe the phenotypic and functional alterations of ILC3s in IBD and discuss the therapeutic potential of ILC3s in the treatment of IBD.

Highlights

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the bowel comprising ulcerative colitis (UC) and Crohn’s disease (CD)
Promotes ILC3s population and function Controls a proliferative balance between ILC3s and ILC2s Controls formation of solitary intestinal lymphoid tissue postnatally Regulates the postnatal differentiation of intestinal ILC3s Regulates homing receptor switch in ILC3s, and thereby regulates the migration of ILC3s to the gut Accelerates the differentiation of human ILC1s to IL-22-producing ILC3s driven by IL-2, IL-1b and IL-23
Exposure to TCDD during pregnancy and lactation in mice led to reduced frequency of colonic ILC3s and decreased expression of receptor gamma t (RORgt) in colonic ILC3s, and increased frequency of colonic NKp46+ILC3 in offspring [38]. These results suggest that environment cues in pregnancy can modulate ILC3 biology in offspring. These findings suggest that host nutritional status can regulate the numbers and function of ILC3s, immune response and susceptibility to colitis, dietary refinements and nutrient supplementation may be beneficial in alleviating the severity of IBD

Summary

INTRODUCTION

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the bowel comprising ulcerative colitis (UC) and Crohn’s disease (CD). An in vitro study revealed that 1a, 25-dihydroxy vitamin D3 (1,25D3), the active form of vitamin D, downregulates the IL-23 receptor pathway in human NKp44+ ILC3s, inhibiting IL-22 and GM-CSF production and inversely enhancing IL-6 production, which encourages ILC3s to maintain an innate-like cytokine expression profile [27]. These results suggest vitamin D is necessary for development and function of ILC3s at steady state, and can restrain the pro-inflammatory properties of ILC3s. RA can accelerate the differentiation of human CD127+ILC1s into IL-22-producing ILC3s in the presence of IL-2, IL-1b and IL-23 [33]

Vitamin A Retinoic acid

Mouse In vivo

REGULATION OF OTHER METABOLITES

CONCLUSIONS