title: Regulation of the mucosal phenotype in dendritic cells by PPARγ: role of tissue microenvironment.
abstract: 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 PPARγ contributes to the development of the "mucosal" phenotype in mouse DCs. Experiments demonstrated that PPARγ 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 PPARγ 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 PPARγ increased the ability of BMDCs to induce T cell-independent IgA production in B cells. BMDCs from PPARγ(ΔDC) mice displayed enhanced expression of costimulatory molecules, enhanced proinflammatory cytokine production, and decreased IL-10 synthesis. Contrary to the inflammatory BMDC phenotype in vitro, PPARγ(ΔDC) mice showed no change in the frequency or phenotype of mDC in the colon. In contrast, mDCs in the lungs were increased significantly in PPARγ(ΔDC) mice. A modest increase in colitis severity was observed in DSS-treated PPARγ(ΔDC) mice compared with control. These results indicate that PPARγ activation induces a mucosal phenotype in mDCs and that loss of PPARγ promotes an inflammatory phenotype. However, the intestinal microenvironment in vivo can maintain the mucosal DC phenotype of via PPARγ-independent mechanisms.
authors.affiliation: 1.Immunology and Molecular Genetics, University of Kentucky, 800 Rose St., Room MS419, Lexington, KY 40536-0298, USA. dcohen@uky.edu.
authors.forename: Halide
authors.initials: H
authors.lastname: Tuna
authors.forename: Rita G
authors.initials: RG
authors.lastname: Avdiushko
authors.forename: Vishal J
authors.initials: VJ
authors.lastname: Sindhava
authors.forename: Leia
authors.initials: L
authors.lastname: Wedlund
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Kaetzel
authors.forename: Alan M
authors.initials: AM
authors.lastname: Kaplan
authors.forename: Subbarao
authors.initials: S
authors.lastname: Bondada
authors.forename: Donald A
authors.initials: DA
authors.lastname: Cohen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D060833:Cellular Microenvironment / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D047495:PPAR gamma
keywords: colitis; homeostasis; immunoregulation