Homeostatic (IL-7) and effector (IL-17) cytokines as... : Current Opinion in Gastroenterology (original) (raw)

Inflammatory bowel disease: Edited by Claudio Fiocchi

Homeostatic (IL-7) and effector (IL-17) cytokines as distinct but complementary target for an optimal therapeutic strategy in inflammatory bowel disease

Kanai, Takanoria; Nemoto, Yasuhirob; Kamada, Nobuhikoa; Totsuka, Terujib; Hisamatsu, Tadakazua; Watanabe, Mamorub; Hibi, Toshifumia

aDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan

bDepartment of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

Correspondence to Dr Takanori Kanai, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan Tel: +81 3 3353 1211; fax: +81 3 3341 3631; e-mail: [email protected]

Abstract

Purpose of review

This review focuses on CD4+ T cells involved in the mediation of inflammatory tissue damage in murine models of inflammatory bowel diseases (IBDs). In particular, we describe the distinct roles of the homeostatic cytokine IL-7, which is essential to the maintenance of colitogenic memory CD4+ cells, and the newly discovered effector cytokine IL-17. We also discuss the close correlation between colitogenic Th17-type CD4+ T cells and inducible CD4+CD25+Foxp3+ regulatory T cells.

Recent findings

IBDs are characterized by wasting and chronic intestinal inflammation induced by many different cytokine-mediated pathways. It is clearly recognized that medical and surgical interventions do not cure Crohn's disease because relapse is the rule after remission. Until a few years ago, IBD was classified into Th1-dependent, that is, Crohn's disease, and Th2-dependent, that is, ulcerative colitis, phenotypes. However, in recent years, it has been shown that new T-cell subclasses, that is, Th17 and regulatory T cells (TR), exist independently of Th1 and Th2 and that they play a central role in modulating IBD.

Summary

The persistence of IL-7-dependent colitogenic memory CD4+ T cells is critical to the maintenance of experimental colitis. On the other hand, though Th1 and Th2 colitogenic memory CD4+ cells exist, in recent years the central role of IL-17-producing Th17-type cells in IBD has attracted renewed interest. The development of molecularly targeted therapies aimed at a variety of different Th-dependent pathogenic mechanisms may represent a novel approach to IBD therapy.