| First Author | Simon JM | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 8 | Pages | 1912-25 |
| PubMed ID | 27159132 | Mgi Jnum | J:246954 |
| Mgi Id | MGI:5922207 | Doi | 10.1002/eji.201546237 |
| Citation | Simon JM, et al. (2016) Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses. Eur J Immunol 46(8):1912-25 |
| abstractText | Intestinal macrophages (IMs) are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters IM programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient (Il10(-/-) ) mice. We identified chromatin accessibility changes associated with bacterial exposure and IL-10 deficiency in both bone marrow derived macrophages and IMs. Surprisingly, Il10(-/-) IMs adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, when recombinant IL-10 was added to Il10(-/-) cells, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model in which IL-10-deficiency leads to chromatin alterations that contribute to a loss of IM tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation. |
