title: Homeostatic (IL-7) and effector (IL-17) cytokines as distinct but complementary target for an optimal therapeutic strategy in inflammatory bowel disease.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. takagast@sc.itc.keio.ac.jp
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.forename: Teruji
authors.initials: T
authors.lastname: Totsuka
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hisamatsu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000818:Animals; D015331:Cohort Studies; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012680:Sensitivity and Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D015851:Interleukin-7