title: CCL22-producing CD8α- myeloid dendritic cells mediate regulatory T cell recruitment in response to G-CSF treatment.
abstract: G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local recruitment of T regulatory cells (Tregs). This is an indirect effect because adoptive transfer of G-CSF-induced tolerogenic dendritic cells (DCs) promotes Treg accumulation. However, the identity of the particular DC subset and the molecule(s) mediating this effect remain unknown. We demonstrate in this study that the adoptive transfer of CD11c(high)CD8α(-) DCs isolated from pegylated G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the pancreatic recruitment of CD4(+)CD25(+)Foxp3(+) Tregs, which generated increased amounts of TGF-β. Likewise, only CD11c(high)CD8α(-) DCs from pegG-CSF recipients secreted the chemokine CCL22 at levels that effectively attracted Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes compared with those from the spleen. Accordingly, CD11c(high)CD8α(-) DCs from the pancreatic lymph nodes of pegG-CSF recipients were more efficient than their splenic counterparts in the recruitment of Tregs upon adoptive transfer. Predictably, CD11c(high)CD8α(-) DCs failed to recruit these Tregs both in vivo and in vitro following intracellular neutralization of CCL22. These data assign a key role to CD8α(-) DCs and CCL22 in Treg recruitment in the protection of NOD mice against type 1 diabetes following the treatment with G-CSF.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8147, 75015 Paris, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Layseca-Espinosa
authors.forename: Sarantis
authors.initials: S
authors.lastname: Korniotis
authors.forename: Ruddy
authors.initials: R
authors.lastname: Montandon
authors.forename: Christophe
authors.initials: C
authors.lastname: Gras
authors.forename: Marie
authors.initials: M
authors.lastname: Bouillié
authors.forename: Roberto
authors.initials: R
authors.lastname: Gonzalez-Amaro
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.forename: Flora
authors.initials: F
authors.lastname: Zavala
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016179:Granulocyte Colony-Stimulating Factor