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Datasets  >  preclinical study dataset  >  Role of IL-10 and IDO in re...

Role of IL-10 and IDO in relation to Th1 and inflammatory responses in colitis model

preclinical study dataset

Our lab has obtained data on the role of IL-10 and IDO in relation to Th1 and inflammatory responses in a colitis model tested on mice. IDO appears critical for the regulation of TNBS colitis upon CTLA-4 engagement, as the beneficial effect of anti-CTLA-4 treatment was lost in IDO-deficient mice. By contrast, the absence of IDO did not alter the course of inflammation in mice injected with TNBS only, an unexpected finding which suggests that IDO-dependent counter-regulation requires other factors/cells in addition to IDO production and T cell activation by TNBS. Our observations would suggest a critical role for activated Treg, producing IL-10 and expressing high levels of CTLA-4, ICOS and FoxP3.

We have investigated the respective role of IL-10 and IDO, both required for Th1 suppression in this model. As IL-10 has been shown to indirectly dampen Th1 responses through the inhibition of IL-12 production by antigen-presenting-cells, we monitored mRNA expression specific for the inducible chain IL-12 p35 in lymph nodes draining the site of injection or in mesenteric lymph nodes of mice instilled intra-colonically with TNBS. Our results clearly show that IL-12 production early after the onset of the response was unaffected by anti-CTLA-4 treatment. By contrast, our data confirm previous data showing that IL-10 is critical for IDO production by DC in vitro, suggesting that IL-10 may act upstream by modulating the expression of IDO. As IDO expression was detected in the colon but not in the spleen or mesenteric lymph nodes, we postulate that IDO may act as anti-inflammatory agent in the intestine and that IL-10 may inhibit Th1 activation in the lymphoid organs and enhance IDO expression in the gut.

We will complete these experiments by (1) testing whether IL-10 is required for IDO expression in vivo; (2) evaluating the role of ICOShi regulatory T cells in the intestine in steady state conditions and (3) the role of intestinal flora in the development of these cells using axenic mice. In parallel, we are testing whether the population of natural regulatory T cells (CD25+) control immune responses by acting on antigen-presenting-cells and in particular on dendritic cells.

created over 15 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF Rdf ]   [ RelFinder Relfinder ]