Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease

Kugathasan, S.; Saubermann, L. J.; Smith, L.; Kou, D.; Itoh, J.; Binion, D. C.; Levine, A. D.; Blumberg, R. S.; Fiocchi, C.
December 2007
Gut;Dec2007, Vol. 56 Issue 12, p1696
Academic Journal
Background and aims: Crohn's disease is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of the pathogenesis is limited because it is based on data from adults with chronic Crohn's disease. We investigated mucosal T-cell immunoregulatory events in children with early Crohn's disease. Methods: Mucosal biopsies and T-cell clones were derived from children experiencing the first attack of Crohn's disease, children with long-standing Crohn's disease, infectious colitis, and children without gut inflammation. Results: As in acute infectious colitis, interleukin (IL) 12 induced T cells from early Crohn's disease to acquire a strongly polarised T helper (Th) type 1 response characterised by high IFN-γ production and IL12Rβ2 chain expression. Th1 polarisation was not induced in clones from late Crohn's disease. Mucosal levels of IL12p40 and IL12Rβ2 messenger RNA were significantly higher in children with early than late Crohn's disease. These results demonstrate that susceptibility to IL12-mediated modulation is strongly dependent on the stage of Crohn's disease. Conclusions: At the onset of Crohn's disease mucosal T cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to late Crohn's disease. This suggests that mucosal T-cell immunoregulation varies with the course of human IBD. Patients with the initial manifestations of IBD may represent an ideal population in which immunomodulation may have optimal therapeutic efficacy.


Related Articles

  • The ATG16L1 Gene Variants rs2241879 and rs2241880 (T300A) Are Strongly Associated With Susceptibility to Crohn's Disease in the German Population. Glas, Jürgen; Konrad, Astrid; Schmechel, Silke; Dambacher, Julia; Seiderer, Julia; Schroff, Frieder; Wetzke, Martin; Roeske, Darina; Török, Helga-Paula; Tonenchi, Laurian; Pfennig, Simone; Haller, Dirk; Griga, Thomas; Klein, Wolfram; Epplen, Jörg T.; Folwaczny, Christian; Lohse, Peter; Göke, Burkhard; Ochsenkühn, Thomas; Mussack, Thomas // American Journal of Gastroenterology;Mar2008, Vol. 103 Issue 3, p682 

    OBJECTIVES: We analyzed ATG16L1, a recently identified Crohn's disease (CD) susceptibility gene, in a large cohort with inflammatory bowel disease (IBD) including potential interactions with other IBD genes as well as factors regulating its gene expression. METHODS: Genomic DNA from 2,890...

  • Inflammatory Bowel Disease: Its Present and Its Future. Kirsner, Joseph B. // American Journal of Gastroenterology;Nov1989, Vol. 84 Issue 11, p1358 

    Discusses the developments in the treatment of inflammatory bowel disease (IBD) as of 2005. Experiment done to determine the treatment for IBD; Pathogenesis of IBD; Microbial cause of IBD.

  • Osteopontin: a new addition to the constellation of cytokines which drive T helper cell type 1 responses in Crohn's disease. Gordon, J. N.; MacDonald, T. T. // Gut;Sep2005, Vol. 54 Issue 9, p1213 

    Presents the author's comments on the role of osteopontin in Crohn's disease. Causes of Crohn's disease; Information on cytokines involved in Crohn's disease; Functions of osteopontin in the body; Importance of plasma cells in inflammatory bowel disease.

  • Impaired Peripheral Th1 CD4+ T Cell Response to Escherichia coli Proteins in Patients with Crohn's Disease and Ankylosing Spondylitis. Ergin, Asgar; Syrbe, Uta; Scheer, Rebecca; Thiel, Andreas; Adam, Thomas; Büssow, Konrad; Duchmann, Rainer; Zeitz, Martin; Sieper, Joachim // Journal of Clinical Immunology;Dec2011, Vol. 31 Issue 6, p998 

    Background: To clarify the impact of T cell responses towards enteric antigens for chronic intestinal inflammation, we determined T helper 1 reactivity towards conserved Escherichia coli proteins in patients with Crohn's disease (CD) and healthy individuals and patients with ankylosing...

  • Immunoregulatory cytokines and intestinal inflammation. Mitsuyama, Keiichi; Toyonaga, Atsushi; Sata, Michio // Journal of Gastroenterology;Feb2005, Vol. 40 Issue 2, p217 

    The article focuses on the expression of immunoregulatory cytokines in inflammatory bowel disease (IBD). There is strong evidence that the abnormal expression and responses of immunoregulatory cytokines, including interleukin (IL)-2, IL-7, and IL-15, are involved in IBD pathogenesis. IL-2 is a...

  • CCR2 expressing CD4+ T lymphocytes are preferentially recruited to the Ileum in Crohn's disease. Connor, S. J.; Paraskevopoulos, N.; Newman, R.; Cuan, N.; Hampartzoumian, T.; Lloyd, A. R.; Grimm, M. C. // Gut;Sep2004, Vol. 53 Issue 9, p1287 

    Background and aims: Chemokine receptors are key determinants of leucocyte trafficking. While the chemokine receptor CCR9 and its chemokine ligand CCL25 (TECK) mediate lymphocyte homing to the healthy small intestine, the chemokine receptors important for recruitment during intestinal...

  • Dichotomy between Lactobacillus rhamnosus and Klebsiella pneumoniae on dendritic cell phenotype and function. Braat, Henri; de Jong, Esther C.; van den Brande, Jan M. H.; Kapsenberg, Martien L.; Peppelenbosch, Maikel P.; van Tol, Eric A. F.; van Deventer, Sander J. H. // Journal of Molecular Medicine;Mar2004, Vol. 82 Issue 3, p197 

    The reaction of the intestinal immune system to intestinal bacteria shows striking differences between various bacterial strains. Whereas Klebsiella pneumoniae induces a fierce proinflammatory reaction, the probiotic strain Lactobacillus rhamnosus has clear anti-inflammatory effect in...

  • NOD2/CARD15 Genotype and Phenotype Differences between Ashkenazi and Sephardic Jews with Crohn's Disease. Karban, Amir; Waterman, Matti; Panhuysen, Carolien I.; Pollak, Rivka Dresner; Nesher, Shula; Datta, Lisa; Weiss, Batia; Suissa, Alain; Shamir, Raanan; Brant, Steven R.; Eliakim, Rami // American Journal of Gastroenterology;Jun2004, Vol. 99 Issue 6, p1134 

    OBJECTIVE: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as...

  • Inflammatory Bowel Diseases.  // Current Medical Literature: Gastroenterology;2009, Vol. 28 Issue 2, p43 

    The article discusses several research on inflammatory bowel diseases. The effectiveness of maintenance treatment of collagenous colitis with oral budesonide was investigated by two studies, one of which took place in Germany while the other was conducted in Denmark. A study in Cork, Ireland...


Read the Article


Sign out of this library

Other Topics