Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses

Eur J Immunol. 2016 Aug;46(8):1912-25. doi: 10.1002/eji.201546237. Epub 2016 Jun 1.


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.

Keywords: Chromatin accessibility; Chronic inflammation; IL-10; Inflammatory bowel disease; Macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism*
  • Cytokines / metabolism
  • Electrophoretic Mobility Shift Assay
  • Gene Expression
  • Humans
  • Immune Tolerance
  • Inflammation / immunology*
  • Interleukin-10 / genetics*
  • Intestines / immunology
  • Intestines / physiopathology*
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Chromatin
  • Cytokines
  • IL10 protein, human
  • IL10 protein, mouse
  • Interleukin-10