title: CD8α⁺β⁻ and CD8α⁺β⁺ plasmacytoid dendritic cells induce Foxp3⁺ regulatory T cells and prevent the induction of airway hyper-reactivity.
abstract: Dendritic cells (DCs) control the balance between protection against pathogens and tolerance to innocuous or self-antigens. Here, we demonstrate for the first time that mouse plasmacytoid DCs (pDCs) can be segregated into three distinct populations, exhibiting phenotypic and functional differences, according to their surface expression of CD8α or CD8β as CD8α⁻β⁻, CD8α⁺β⁻, or CD8α⁺β⁺. In a mouse model of lung inflammation, adoptive transfer of CD8α⁺β⁻ or CD8α⁺β⁺ pDCs prevents the development of airway hyper-reactivity. The tolerogenic features of these subsets are associated with increased production of retinoic acid, which leads to the enhanced induction of Foxp3⁺ regulatory T cells compared with CD8α⁻β⁻ pDCs. Our data thus identify subsets of pDCs with potent tolerogenic functions that may contribute to the maintenance of tolerance in mucosal sites such as the lungs.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: V
authors.initials: V
authors.lastname: Lombardi
authors.forename: A O
authors.initials: AO
authors.lastname: Speak
authors.forename: J
authors.initials: J
authors.lastname: Kerzerho
authors.forename: N
authors.initials: N
authors.lastname: Szely
authors.forename: O
authors.initials: O
authors.lastname: Akbari
mesh_terms: D019264:Adoptive Transfer; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007108:Immune Tolerance / Q000276:immunology; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000941:Antigens; D016827:CD8 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000444:Aldehyde Dehydrogenase