JOURNAL ARTICLE

Commensal gut flora reduces susceptibility to experimentally induced colitis via T-cell-derived interleukin-10

Marina C Pils, André Bleich, Immo Prinz, Nicolas Fasnacht, Mariela Bollati-Fogolin, Angela Schippers, Björn Rozell, Werner Müller
Inflammatory Bowel Diseases 2011, 17 (10): 2038-46
21182023

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.

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