| First Author | Tuna H | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 3 | Pages | 471-85 |
| PubMed ID | 24295831 | Mgi Jnum | J:211879 |
| Mgi Id | MGI:5576836 | Doi | 10.1189/jlb.0713408 |
| Citation | Tuna H, et al. (2014) Regulation of the mucosal phenotype in dendritic cells by PPARgamma: role of tissue microenvironment. J Leukoc Biol 95(3):471-85 |
| abstractText | Mucosal DCs play a critical role in tissue homeostasis. Several stimuli can induce a mucosal phenotype; however, molecular pathways that regulate development of mucosal DC function are relatively unknown. This study sought to determine whether PPARgamma contributes to the development of the "mucosal" phenotype in mouse DCs. Experiments demonstrated that PPARgamma activation in BMDCs induced an immunosuppressive phenotype in which BMDCs had reduced expression of MHC class II and costimulatory molecules, increased IL-10 secretion, and reduced the ability to induce CD4 T cell proliferation. Activation of PPARgamma enhanced the ability of BMDC to polarize CD4 T cells toward iTregs and to induce T cell expression of the mucosal homing receptor, CCR9. Activation of PPARgamma increased the ability of BMDCs to induce T cell-independent IgA production in B cells. BMDCs from PPARgamma(DeltaDC) mice displayed enhanced expression of costimulatory molecules, enhanced proinflammatory cytokine production, and decreased IL-10 synthesis. Contrary to the inflammatory BMDC phenotype in vitro, PPARgamma(DeltaDC) mice showed no change in the frequency or phenotype of mDC in the colon. In contrast, mDCs in the lungs were increased significantly in PPARgamma(DeltaDC) mice. A modest increase in colitis severity was observed in DSS-treated PPARgamma(DeltaDC) mice compared with control. These results indicate that PPARgamma activation induces a mucosal phenotype in mDCs and that loss of PPARgamma promotes an inflammatory phenotype. However, the intestinal microenvironment in vivo can maintain the mucosal DC phenotype of via PPARgamma-independent mechanisms. |
