title: Modulation of regulatory T cell-Th17 balance by plasmacytoid dendritic cells.
abstract: Tregs represent an interesting therapeutic tool to modulate immune responses that could be deleterious in autoimmune diseases and in transplantation. However, phenotype and functions of Tregs do not seem to be stable, and recent data suggest that FoxP3-expressing Tregs can be driven to produce IL-17. In this study, we have analyzed the role of pDCs versus cDCs on Treg responses and underlined that pDCs have an intrinsic, unique capacity to induce IL-17 secretion from T cells. We showed in rats that FoxP3(+) Tregs were able to secrete IL-17 only when stimulated by allogeneic, mature pDCs but not cDCs. In addition, in rats and mice, mature pDCs but not cDCs inhibited in vitro Treg-suppressive functions and in the presence of Tregs, supported Th17 differentiation from naive T cells through secretion of high amounts of IL-6. These data suggest an important role for pDCs in modulating or switching Treg function and allowing Th17 differentiation.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, UMR 643, Nantes, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gautreau
authors.forename: Dominique
authors.initials: D
authors.lastname: Chabannes
authors.forename: Michèle
authors.initials: M
authors.lastname: Heslan
authors.forename: Régis
authors.initials: R
authors.lastname: Josien
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6