| First Author | Patik I | Year | 2023 |
| Journal | Mucosal Immunol | Volume | 16 |
| Issue | 3 | Pages | 233-249 |
| PubMed ID | 36868479 | Mgi Jnum | J:338077 |
| Mgi Id | MGI:7510042 | Doi | 10.1016/j.mucimm.2023.02.006 |
| Citation | Patik I, et al. (2023) The IL-10 receptor inhibits cell extrinsic signals necessary for STAT1-dependent macrophage accumulation during colitis. Mucosal Immunol 16(3):233-249 |
| abstractText | The loss of IL-10R function leads to severe early onset colitis and, in murine models, is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed, STAT1(-/-) mice exhibit defects in colonic macrophage accumulation after Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNgammaR, an inducer of STAT1 activation. Radiation chimeras demonstrated that reduced accumulation of STAT1-deficient macrophages was based on a cell-intrinsic defect. Unexpectedly, mixed radiation chimeras generated with both wild-type and IL-10R-deficient bone marrow indicated that rather than directly interfering with STAT1 function, IL-10R inhibits the generation of cell extrinsic signals that promote the accumulation of immature macrophages. These results define the essential mechanisms controlling the inflammatory macrophage accumulation in inflammatory bowel diseases. |
