| First Author | Hontecillas R | Year | 2011 |
| Journal | Mucosal Immunol | Volume | 4 |
| Issue | 3 | Pages | 304-13 |
| PubMed ID | 21068720 | Mgi Jnum | J:287901 |
| Mgi Id | MGI:6407554 | Doi | 10.1038/mi.2010.75 |
| Citation | Hontecillas R, et al. (2011) Immunoregulatory mechanisms of macrophage PPAR-gamma in mice with experimental inflammatory bowel disease. Mucosal Immunol 4(3):304-13 |
| abstractText | Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IBD. This study aimed to characterize the mechanisms underlying the beneficial effects of macrophage PPAR-gamma in IBD. Macrophage-specific PPAR-gamma deletion significantly exacerbated clinical activity and colonic pathology, impaired the splenic and mesenteric lymph node regulatory T-cell compartment, increased percentages of lamina propria (LP) CD8+ T cells, increased surface expression of CD40, Ly6C, and Toll-like receptor 4 (TLR-4) in LP macrophages, and upregulated expression of colonic IFN-gamma, CXCL9, CXCL10, IL-22, IL1RL1, CCR1, suppressor of cytokine signaling 3, and MHC class II in mice with IBD. Moreover, macrophage PPAR-gamma was required for accelerating pioglitazone-mediated recovery from dextran sodium sulfate (DSS) colitis, providing a cellular target for the anti-inflammatory effects of PPAR-gamma agonists in IBD. |
