title: An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.
abstract: OBJECTIVE
  Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease.
  
  
  METHODS
  Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic for an anti-ovalbumin T-cell receptor or an anti-hen egg lysozyme B-cell receptor were studied. Adoptive transfers were performed of T or B cells or both from nuclear factor of activated T cells c2-deficient mice into nuclear factor of activated T cells c2-deficient recombinase activating gene-deficient animals, in the presence or absence of antibodies that neutralize interleukin-10 activity.
  
  
  RESULTS
  Nuclear factor of activated T cells c2-deficient, recombinase activating gene-deficient animals spontaneously developed a severe inflammatory bowel syndrome that resembled ulcerative colitis but was composed entirely of nonlymphocytes. The disease was suppressed by the adoptive transfer of polyclonal B-cell populations, even on neutralization of interleukin-10, but not by the presence of monoclonal T or B cells.
  
  
  CONCLUSIONS
  Nuclear factor of activated T cells plays a critical role in the regulation of bowel inflammation by nonlymphoid immune cells, and B cells suppress bowel inflammation by innate immune cells. Such findings indicate a novel, interleukin-10-independent role for nuclear factor of activated T cells in the regulation of innate immunity and in intestinal immune tolerance.
authors.affiliation: Department of Internal Medicine/Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Gerth
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Stanford L
authors.initials: SL
authors.lastname: Peng
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012005:Rectal Prolapse / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D009687:Nuclear Proteins; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2