title: A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.
abstract: Foxp3+regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43+CCR5+Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43+CCR5+CXCR3-Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.|Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, 584-8540, Japan.|Japan Society for the Promotion of Science, Japan.
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.affiliation: Quantitative Immunology Research Unit, IFReC, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Teraguchi
authors.affiliation: Immuno-Genomics Research Unit, IFReC, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vandenbon
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.|Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Francis H W
authors.initials: FH
authors.lastname: Shand
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: The Tazuke-Kofukai Medical Research Institute, Kitano Hospital, Kita-ku, Osaka, 530-8480, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.|Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, 584-8540, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D053804:Granzymes / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D051917:Leukosialin / Q000378:metabolism; D051379:Mice; D019713:Receptors, CCR5 / Q000378:metabolism; D059010:Single-Cell Analysis; D012867:Skin; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C584933:CCR5 protein, human; C508609:IL10 protein, human; D051917:Leukosialin; D019713:Receptors, CCR5; C465014:SPN protein, human; D016753:Interleukin-10; C509213:GZMB protein, human; D053804:Granzymes