2014-05-15
Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function
Publication
Publication
Immunity , Volume 40 - Issue 5 p. 706- 719
Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on Tcells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4+ Tcell transfer, Rag2-/-Il10rb-/- mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb-/- anti-inflammatory macrophages ameliorated colitis induction by WT CD4+ Tcells in Rag2-/-Il10rb-/- mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.
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| doi.org/10.1016/j.immuni.2014.03.011, hdl.handle.net/1765/55291 | |
| Immunity | |
| Organisation | Department of Pediatrics |
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Shouval, D., Biswas, R., Goettel, J., McCann, K., Conaway, E., Redhu, N., Mascanfroni, I., AlAdham, Z., Lavoie, S., Ibourk, M., Nguyen, D., Samsom, J., Escher, J., Somech, R., Weiss, B., Beier, R., Conklin, L., Ebens, C., Santos, F., … Snapper, S. (2014). Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity, 40(5), 706–719.https://doi.org/10.1016/j.immuni.2014.03.011 |
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