Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice.

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  • Additional Information
    • Source:
      Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0012 (Electronic) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE
    • Publication Information:
      Publication: Philadelphia, PA : W.B. Saunders
      Original Publication: Baltimore.
    • Subject Terms:
      Colitis/*genetics ; Colitis/*metabolism ; Mutation/*genetics ; Receptors, Antigen, T-Cell, alpha-beta/*metabolism ; Receptors, Antigen, T-Cell, gamma-delta/*metabolism ; T-Lymphocytes/*metabolism; Animals ; Chronic Disease ; Colitis/pathology ; Colon/metabolism ; Colon/pathology ; Disease Models, Animal ; Homeostasis ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophils/pathology ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Severity of Illness Index ; Signal Transduction/physiology ; T-Lymphocytes/pathology
    • Abstract:
      Background & Aims: T-cell receptor (TCR) gammadelta T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in gammadelta T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of gammadelta T cells in chronic colitis has not been fully identified.
      Methods: TCRalpha-deficient mice, which spontaneously develop chronic colitis with many features of human UC including an increase in gammadelta T-cell population, represent an excellent model to investigate the role of gammadelta T cells in UC-like colitis. To identify the role of gammadelta T cells in this colitis, we herein have generated TCRgamma-deficient mice through deletion of all TCR Cgamma genes (Cgamma1, Cgamma2, Cgamma3, and Cgamma4) using the Cre/loxP site-specific recombination system and subsequently crossing these mice with TCRalpha-deficient mice.
      Results: An increase in colonic gammadelta T cells was associated with the development of human UC as well as UC-like disease seen in TCRalpha-deficient mice. Interestingly, the newly established TCRalpha(-/-) x TCRgamma(-/-) double mutant mice developed significantly less severe colitis as compared with TCRalpha-deficient mice. The suppression of colitis in TCRalpha(-/-) x TCRgamma(-/-) double mutant mice was associated with a significant reduction of proinflammatory cytokine and chemokine productions and a decrease in neutrophil infiltration.
      Conclusions: gammadelta T cells are involved in the exacerbation of UC-like chronic disease. Therefore, gammadelta T cells may represent a promising therapeutic target for the treatment of human UC.
    • Grant Information:
      DK064351 United States DK NIDDK NIH HHS; DK47677 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Receptors, Antigen, T-Cell, alpha-beta)
      0 (Receptors, Antigen, T-Cell, gamma-delta)
    • Publication Date:
      Date Created: 20080205 Date Completed: 20080214 Latest Revision: 20220330
    • Publication Date:
      20221213
    • Accession Number:
      10.1053/j.gastro.2007.11.056
    • Accession Number:
      18242214