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

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 (T-R), 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.