title: IL10-Deficiency in CD4⁺ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis.
abstract: OBJECTIVE
  IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation.
  
  
  METHODS
  Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C.) rodentium and analyzed for the specific immune response and pathogloy in the colon.
  
  
  RESULTS
  We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon.
  
  
  CONCLUSIONS
  Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.
authors.forename: Virginia
authors.initials: V
authors.lastname: Seiffart
authors.forename: Julia
authors.initials: J
authors.lastname: Zoeller
authors.forename: Robert
authors.initials: R
authors.lastname: Klopfleisch
authors.forename: Munisch
authors.initials: M
authors.lastname: Wadwa
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Christian
authors.initials: C
authors.lastname: Riedel
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D044082:Citrobacter rodentium / Q000276:immunology*; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004756:Enterobacteriaceae Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017353:Gene Deletion; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma