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Article

Human Keratinocytes Inhibit CD4+ T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints

1
CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France
2
Université Paris-Saclay, 91190 Saint-Aubin, France
3
CEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, France
4
U976 HIPI Unit, IRSL, Université Paris, 75010 Paris, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this article.
Academic Editor: Cord Brakebusch
Cells 2021, 10(6), 1438; https://doi.org/10.3390/cells10061438
Received: 10 May 2021 / Revised: 3 June 2021 / Accepted: 4 June 2021 / Published: 8 June 2021
(This article belongs to the Special Issue Molecular Determinants of Skin Integrity)
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. View Full-Text
Keywords: skin immunity; human keratinocytes; immunomodulation; HLA-G1; PD-L1; TGFB1; tolerance skin immunity; human keratinocytes; immunomodulation; HLA-G1; PD-L1; TGFB1; tolerance
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MDPI and ACS Style

Mestrallet, G.; Auvré, F.; Schenowitz, C.; Carosella, E.D.; LeMaoult, J.; Martin, M.T.; Rouas-Freiss, N.; Fortunel, N.O. Human Keratinocytes Inhibit CD4+ T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints. Cells 2021, 10, 1438. https://doi.org/10.3390/cells10061438

AMA Style

Mestrallet G, Auvré F, Schenowitz C, Carosella ED, LeMaoult J, Martin MT, Rouas-Freiss N, Fortunel NO. Human Keratinocytes Inhibit CD4+ T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints. Cells. 2021; 10(6):1438. https://doi.org/10.3390/cells10061438

Chicago/Turabian Style

Mestrallet, Guillaume, Frédéric Auvré, Chantal Schenowitz, Edgardo D. Carosella, Joel LeMaoult, Michèle T. Martin, Nathalie Rouas-Freiss, and Nicolas O. Fortunel 2021. "Human Keratinocytes Inhibit CD4+ T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints" Cells 10, no. 6: 1438. https://doi.org/10.3390/cells10061438

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