Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
Guillaume Mestrallet,
Frédéric Auvré,
Chantal Schenowitz,
Edgardo D. Carosella,
Joel LeMaoult,
Michèle T. Martin,
Nathalie Rouas-Freiss,
Nicolas O. Fortunel
Affiliations
Guillaume Mestrallet
CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France
Frédéric Auvré
CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France
Chantal Schenowitz
CEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, France
Edgardo D. Carosella
CEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, France
Joel LeMaoult
CEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, France
Michèle T. Martin
CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France
Nathalie Rouas-Freiss
CEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, France
Nicolas O. Fortunel
CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France
Human skin protects the body against infection and injury. This protection involves immune and epithelial cells, but their interactions remain largely unknown. Here, we show that cultured epidermal keratinocytes inhibit allogenic CD4+ T-cell proliferation under both normal and inflammatory conditions. Inhibition occurs through the secretion of soluble factors, including TGFB1 and the cell-surface expression of HLA-G1 and PD-L1 immune checkpoints. For the first time, we here describe the expression of the HLA-G1 protein in healthy human skin and its role in keratinocyte-driven tissue immunomodulation. The overexpression of HLA-G1 with an inducible vector increased the immunosuppressive properties of keratinocytes, opening up perspectives for their use in allogeneic settings for cell therapy.
