| First Author | Mencarelli A | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1102 |
| PubMed ID | 29549257 | Mgi Jnum | J:259703 |
| Mgi Id | MGI:6149319 | Doi | 10.1038/s41467-018-03495-3 |
| Citation | Mencarelli A, et al. (2018) Calcineurin-mediated IL-2 production by CD11c(high)MHCII(+) myeloid cells is crucial for intestinal immune homeostasis. Nat Commun 9(1):1102 |
| abstractText | The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11c(high)MHCII(+) cells (Cnb1 (CD11c) mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3(+) regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11c(high)MHCII(+) cells to express IL-2. Deleting IL-2 in CD11c(high)MHCII(+) cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine. |
