| First Author | Osborne LC | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 5 | Pages | 2292-300 |
| PubMed ID | 23355735 | Mgi Jnum | J:193473 |
| Mgi Id | MGI:5468597 | Doi | 10.4049/jimmunol.1200706 |
| Citation | Osborne LC, et al. (2013) Resistin-like Molecule alpha Promotes Pathogenic Th17 Cell Responses and Bacterial-Induced Intestinal Inflammation. J Immunol 190(5):2292-300 |
| abstractText | Resistin-like molecule (RELM)alpha belongs to a family of secreted mammalian proteins that have putative immunomodulatory functions. Recent studies have identified a pathogenic role for RELMalpha in chemically induced colitis through effects on innate cell populations. However, whether RELMalpha regulates intestinal adaptive immunity to enteric pathogens is unknown. In this study, we employed Citrobacter rodentium as a physiologic model of pathogenic Escherichia coli-induced diarrheal disease, colitis, and Th17 cell responses. In response to Citrobacter, RELMalpha expression was induced in intestinal epithelial cells, infiltrating macrophages, and eosinophils of the infected colons. Citrobacter-infected RELMalpha(-/-) mice exhibited reduced infection-induced intestinal inflammation, characterized by decreased leukocyte recruitment to the colons and reduced immune cell activation compared with wild-type (WT) mice. Interestingly, Citrobacter colonization and clearance were unaffected in RELMalpha(-/-) mice, suggesting that the immune stimulatory effects of RELMalpha following Citrobacter infection were pathologic rather than host-protective. Furthermore, infected RELMalpha(-/-) mice exhibited decreased CD4(+) T cell expression of the proinflammatory cytokine IL-17A. To directly test whether RELMalpha promoted Citrobacter-induced intestinal inflammation via IL-17A, infected WT and IL-17A(-/-) mice were treated with rRELMalpha. RELMalpha treatment of Citrobacter-infected WT mice exacerbated intestinal inflammation and IL-17A expression whereas IL-17A(-/-) mice were protected from RELMalpha-induced intestinal inflammation. Finally, infected RELMalpha(-/-) mice exhibited reduced levels of serum IL-23p19 compared with WT mice, and RELMalpha(-/-) peritoneal macrophages showed deficient IL-23p19 induction. Taken together, these data identify a proinflammatory role for RELMalpha in bacterial-induced colitis and suggest that the IL-23/Th17 axis is a critical mediator of RELMalpha-induced inflammation. |
