title: Commensal gut flora reduces susceptibility to experimentally induced colitis via T-cell-derived interleukin-10.
abstract: BACKGROUND
  Regulatory cytokines are well known to modify experimental colitis in mice. The aim of this study was to elucidate the effect of interleukin (IL)-10 derived from different cellular sources and the effect of commensal gut flora in dextran sulfate sodium (DSS)-induced colitis in mice.
  
  
  METHODS
  Wildtype (WT) and IL-10 deficient (IL-10(-/-) ) mice either harboring a characterized specific pathogen-free (SPF) gut flora or germfree were exposed to 2% DSS. Moreover, cell type-specific IL-10, IL-4, and IL-12 knockout mice and animals combining the T-cell-specific IL-10 knockout with a deficiency in IL-12 or IL-4 were exposed to DSS.
  
  
  RESULTS
  SPF IL-10(-/-) mice showed an increased susceptibility to DSS-induced colitis compared to WT mice determined by histopathology and proinflammatory cytokine and chemokine responses. Under germfree conditions, both WT and IL-10(-/-) mice were highly susceptible to DSS. IL-10 mRNA was increased upon DSS exposure in WT SPF but not in germfree mice. Mice carrying a specific deletion of IL-10 in T-cells exhibited a tendency towards an enhanced susceptibility to DSS. The lack of T-cell-derived IL-10 in combination with the lack of IL-4 increased the susceptibility to DSS colitis, as did the lack of IL-12 alone.
  
  
  CONCLUSIONS
  IL-10 is a crucial factor inhibiting the innate proinflammatory immune response induced by DSS. Intestinal bacteria are necessary for the induction of protective IL-10, which is mainly T-cell-derived. T-cell-derived IL-10 can only mediate its protective effect in a Th1-dominated milieu. If the balance is shifted towards a Th2 response, IL-10 is not protective.
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany. marina.pils@helmholtz-hzi.de
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.forename: André
authors.initials: A
authors.lastname: Bleich
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasnacht
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollati-Fogolin
authors.forename: Angela
authors.initials: A
authors.lastname: Schippers
authors.forename: Björn
authors.initials: B
authors.lastname: Rozell
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D004198:Disease Susceptibility; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007113:Immunity, Innate; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008297:Male; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D016264:Dextran Sulfate