title: Plasmacytoid dendritic cells play a major role in apoptotic leukocyte-induced immune modulation.
abstract: Several APCs participate in apoptotic cell-induced immune modulation. Whether plasmacytoid dendritic cells (PDCs) are involved in this process has not yet been characterized. Using a mouse model of allogeneic bone marrow engraftment, we demonstrated that donor bone marrow PDCs are required for both donor apoptotic cell-induced engraftment and regulatory T cell (Treg) increase. We confirmed in naive mice receiving i.v. syngeneic apoptotic cell infusion that PDCs from the spleen induce ex vivo Treg commitment. We showed that PDCs did not interact directly with apoptotic cells. In contrast, in vivo macrophage depletion experiments using clodronate-loaded liposome infusion and coculture experiments with supernatant from macrophages incubated with apoptotic cells showed that PDCs required macrophage-derived soluble factors--including TGF-β--to exert their immunomodulatory functions. Overall, PDCs may be considered as the major APC involved in Treg stimulation/generation in the setting of an immunosuppressive environment obtained by apoptotic cell infusion. These findings show that like other APCs, PDC functions are influenced, at least indirectly, by exposure to blood-borne apoptotic cells. This might correspond with an additional mechanism preventing unwanted immune responses against self-antigens clustered at the cell surface of apoptotic cells occurring during normal cell turnover.
authors: INSERM Unité Mixte de Recherche 645, F-25020 Besançon Cedex, France.
authors: Francis
authors: F
authors: Bonnefoy
authors: Sylvain
authors: S
authors: Perruche
authors: Mélanie
authors: M
authors: Couturier
authors: Abdeslem
authors: A
authors: Sedrati
authors: Yunwei
authors: Y
authors: Sun
authors: Pierre
authors: P
authors: Tiberghien
authors: Béatrice
authors: B
authors: Gaugler
authors: Philippe
authors: P
authors: Saas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001853:Bone Marrow; D016026:Bone Marrow Transplantation; D004002:Clodronic Acid; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D007165:Immunosuppression Therapy; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D016212:Transforming Growth Factor beta; D004002:Clodronic Acid