Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis.
|
| Abstract |
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 CD11chighMHCII+ 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 CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ 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.
|
|---|---|
| Authors | Andrea Mencarelli, Hanif Javanmard Khameneh, Jan Fric, Maurizio Vacca, Sary El Daker, Baptiste Janela, Jing Ping Tang, Sabrina Nabti, Akhila Balachander, Tong Seng Lim, Florent Ginhoux, Paola Ricciardi-Castagnoli, Alessandra Mortellaro |
| Journal | Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 1102 (03 16 2018) ISSN: 2041-1723 [Electronic] England |
| PMID | 29549257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!