Type 2 immunity in intestinal homeostasis and inflammatory bowel disease.

Xinxin Luo,Eduardo J Villablanca

doi:10.1042/bst20210535

Abstract

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (TH2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

Highlights

The breakdown of intestinal homeostasis may lead to aberrant immune responses against luminal antigens and eventually lead to inflammatory bowel diseases (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC)
Parasite infection known as helminths infection such as intestinal residing hookworm [4] promotes strong type 2 immune responses, wherein T helper 2 cells (TH2) and innate lymphoid cells class 2 (ILC2s) are the major drivers of such responses [5,6]
Despite the primarily role of TH1 immune responses in the establishment of ileitis in SAMP1/YitFc mice, the terminal ileal tissue manifested an elevated type 2 immunity signature (IL-5, IL-13, and GATA3/Tbet ratio) during chronic inflammation compared with the healthy control [23].TH2 responses are the driving force in an oxazolone-induced colitis murine model, which can be attenuated by suppressing type 2 cytokines [24,25,26]

Summary

Review Article

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. Worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); the role of type 2 immune responses in the initiation and progression of IBD is not fully understood.

Introduction

Intestinal epithelial cells

Tuft cell

Findings

Goblet cells