Potential role of Th17 cells in the pathogenesis of inflammatory bowel disease.

The etiopathology of inflammatory bowel disease (IBD) remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation. IBD including Crohn's disease (CD) and ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Th1-mediated inflammatory disorder while UC is regarded as a Th2-like disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Th1 or Th2 cells, and several cytokines [e.g. interleukin (IL)-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.

[1]  R. Coffman,et al.  TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. , 1989, Annual review of immunology.

[2]  T. Sakaguchi,et al.  Claudins regulate the intestinal barrier in response to immune mediators. , 2000, Gastroenterology.

[3]  J. Shellito,et al.  Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense , 2001, The Journal of experimental medicine.

[4]  P. Rutgeerts,et al.  Role of interleukin‐12 in the induction of mucosal inflammation and abrogation of regulatory T cell function in chronic experimental colitis , 2001, European journal of immunology.

[5]  T. Mcclanahan,et al.  A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R1 , 2002, The Journal of Immunology.

[6]  Ying K. Tam,et al.  Cytokines in the generation and maturation of dendritic cells: recent advances. , 2002, European cytokine network.

[7]  R. Kastelein,et al.  Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain , 2003, Nature.

[8]  M. Neurath,et al.  Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. , 2003, The Journal of clinical investigation.

[9]  A. Andoh,et al.  Increased expression of interleukin 17 in inflammatory bowel disease , 2003, Gut.

[10]  A. Andoh,et al.  Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. , 2004, Clinical immunology.

[11]  A. Lindén,et al.  Interleukin-17 family members and inflammation. , 2004, Immunity.

[12]  D. Littman,et al.  Thymic Origin of Intestinal αß T Cells Revealed by Fate Mapping of RORγt+ Cells , 2004, Science.

[13]  R. de Waal Malefyt,et al.  IL‐12 and IL‐23: master regulators of innate and adaptive immunity , 2004, Immunological reviews.

[14]  Ying Wang,et al.  A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 , 2005, Nature Immunology.

[15]  R. Sartor Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[16]  L. Hennighausen,et al.  Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system , 2006, Nature Immunology.

[17]  R. J. Hocking,et al.  TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. , 2006, Immunity.

[18]  R. D. Hatton,et al.  Transforming growth factor-β induces development of the TH17 lineage , 2006, Nature.

[19]  H. Weiner,et al.  Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells , 2006, Nature.

[20]  T. Mcclanahan,et al.  IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. , 2006, The Journal of clinical investigation.

[21]  D. Danilenko,et al.  Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells , 2006, Nature Immunology.

[22]  D. Littman,et al.  The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells , 2006, Cell.

[23]  A. Sher,et al.  IL-23 plays a key role in Helicobacter hepaticus–induced T cell–dependent colitis , 2006, The Journal of experimental medicine.

[24]  V. Kuchroo,et al.  TH-17 cells in the circle of immunity and autoimmunity , 2007, Nature Immunology.

[25]  A. D. Panopoulos,et al.  Essential autocrine regulation by IL-21 in the generation of inflammatory T cells , 2007, Nature.

[26]  Terry B. Strom,et al.  IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells , 2007, Nature.

[27]  T. Mcclanahan,et al.  TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology , 2007, Nature Immunology.

[28]  Fuguang Li,et al.  Blockage of tumor necrosis factor prevents intestinal mucosal inflammation through down-regulation of interleukin-23 secretion. , 2007, Journal of autoimmunity.

[29]  T. Mcclanahan,et al.  Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. , 2007, Gastroenterology.

[30]  R. Kastelein,et al.  Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. , 2007, Annual review of immunology.

[31]  M. Umemura,et al.  Interleukin‐17 as an Effector Molecule of Innate and Acquired Immunity against Infections , 2007, Microbiology and immunology.

[32]  G. Adler,et al.  Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions1 , 2008, The Journal of Immunology.

[33]  Chen Dong,et al.  T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. , 2008, Immunity.

[34]  A. Abbas,et al.  Interleukin‐2 in the development and control of inflammatory disease , 2008, Immunological reviews.

[35]  L. Fouser,et al.  IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. , 2008, The Journal of clinical investigation.

[36]  Wen-rong Gong,et al.  Cutting Edge: IFN-γ Enables APC to Promote Memory Th17 and Abate Th1 Cell Development1 , 2008, The Journal of Immunology.

[37]  B. Müller-Myhsok,et al.  Role of the novel Th17 cytokine IL‐17F in inflammatory bowel disease (IBD): Upregulated colonic IL‐17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD , 2008, Inflammatory bowel diseases.

[38]  S. Targan,et al.  Immunopathogenesis of inflammatory bowel disease. , 2008, World journal of gastroenterology.

[39]  H. Yoshida,et al.  Regulation of immune responses by interleukin‐27 , 2008, Immunological reviews.

[40]  A. Steere,et al.  Borrelia burgdorferi NapA-driven Th17 cell inflammation in lyme arthritis. , 2008, Arthritis and rheumatism.

[41]  R. Wu,et al.  Regulation of airway innate and adaptive immune responses: the IL-17 paradigm. , 2008, Critical reviews in immunology.

[42]  T. Hibi,et al.  IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease , 2008, Gut.

[43]  K. Mills Induction, function and regulation of IL‐17‐producing T cells , 2008, European journal of immunology.

[44]  A. Pernis,et al.  Th17 cells in rheumatoid arthritis and systemic lupus erythematosus , 2009, Journal of internal medicine.

[45]  D. Littman,et al.  Plasticity of CD4+ T cell lineage differentiation. , 2009, Immunity.

[46]  F. Nestle,et al.  The IL-23/Th17 axis in the immunopathogenesis of psoriasis. , 2009, The Journal of investigative dermatology.

[47]  Dan R. Littman,et al.  Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria , 2009, Cell.

[48]  Thomas Korn,et al.  IL-17 and Th17 Cells. , 2009, Annual review of immunology.

[49]  Li V. Yang,et al.  Il‐21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease , 2009, Inflammatory bowel diseases.

[50]  Zhanju Liu,et al.  Current strategies for the treatment of ulcerative colitis. , 2009, Recent patents on inflammation & allergy drug discovery.