Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function
- Shouval, D.S. (Dror)
- Biswas, R.S. (Rajat)
- Goettel, J.A. (Jeremy)
- McCann, K. (Katelyn)
- Conaway, E. (Evan)
- Redhu, N.S. (Naresh)
- Mascanfroni, I.D. (Ivan)
- AlAdham, Z. (Ziad)
- Lavoie, S. (Sydney)
- Ibourk, M. (Mouna)
- Nguyen, D.D. (Deanna)
- Samsom, J.N. (Janneke)
- Escher, J.C. (Johanna)
- Somech, R. (Raz)
- Weiss, B. (Batia)
- Beier, R. (Rita)
- Conklin, L.S. (Laurie)
- Ebens, C.L. (Christen)
- Santos, F.G.M.S. (Fernanda)
- Ferreira, A.R. (Alexandre)
- Sherlock, J.K. (Jon)
- Bhan, A.K. (Atul)
- Müller, W. (Werner)
- Mora, J.R. (J. Rodrigo)
- Quintana, F.J. (Francisco)
- Klein, C. (Christoph)
- Muise, A.M. (Aleixo)
- Horwitz, R.I. (Ralph)
- Snapper, S.B. (Scott)
DOIAbstract
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...
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