title: Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.
abstract: Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.
authors.affiliation: St. John's Institute of Dermatology, King's College London and National Institutes for Health Research Biomedical Research Centre, London, UK.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chu
authors.forename: Niwa
authors.initials: N
authors.lastname: Ali
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.forename: Paola
authors.initials: P
authors.lastname: Di Meglio
authors.forename: Ania
authors.initials: A
authors.lastname: Skowera
authors.forename: Luca
authors.initials: L
authors.lastname: Napolitano
authors.forename: Guillermo
authors.initials: G
authors.lastname: Barinaga
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grys
authors.forename: Ehsan
authors.initials: E
authors.lastname: Sharif-Paghaleh
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Karagiannis
authors.forename: Mark
authors.initials: M
authors.lastname: Peakman
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002762:Cholecalciferol / Q000494:pharmacology; D003872:Dermatitis / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007211:Indoles; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology*; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018180:Thrombomodulin
chemical_list: D000954:Antigens, Surface; D007211:Indoles; D053631:Interleukin Receptor Common gamma Subunit; D018950:Lipopolysaccharide Receptors; C546931:THBD protein, human; D018180:Thrombomodulin; D016753:Interleukin-10; D002762:Cholecalciferol; C007293:DAPI