Macrophage dysfunction initiates colitis during weaning of infant mice lacking the interleukin-10 receptor

Research output: Contribution to journalArticle

  • External authors:
  • Naresh S. Redhu
  • Vasudevan Bakthavatchalu
  • Evan A Conaway
  • Dror S. Shouval
  • Amy M Tsou
  • Jeremy A. Goettel
  • Amlan Biswas
  • Chuanwu Wang
  • Michael Field
  • Andre Bleich
  • Ning Li
  • Georg K Gerber
  • Lynn Bry
  • James G Fox
  • Scott B Snapper
  • Bruce H Horwitz


Infants with defects in the interleukin 10 receptor (IL10R) develop very early onset inflammatory bowel disease. Whether IL10R regulates lamina propria macrophage function during infant development in mice and whether macrophage-intrinsic IL10R signaling is required to prevent colitis in infancy is unknown. Here we show that although signs of colitis are absent in IL10R-deficient mice during the first 2 weeks of life, intestinal inflammation and macrophage dysfunction begin during the 3(rd) week of life, concomitant with weaning and accompanying diversification of the intestinal microbiota. However, IL10R did not directly regulate the microbial ecology during infant development. Interestingly, macrophage depletion with clodronate inhibited the development of colitis, while the absence of IL10R specifically on macrophages sensitized infant mice to the development of colitis. These results indicate that IL10R-mediated regulation of macrophage function during the early postnatal period is indispensable for preventing the development of murine colitis.

Bibliographical metadata

Original languageEnglish
Article numbere27652
Early online date5 Jul 2017
Publication statusPublished - 5 Jul 2017