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

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

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<sup>+</sup> T-cell proliferation under both normal and...

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Main Authors: Guillaume Mestrallet, Frédéric Auvré, Chantal Schenowitz, Edgardo D. Carosella, Joel LeMaoult, Michèle T. Martin, Nathalie Rouas-Freiss, Nicolas O. Fortunel
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cells
Subjects:
skin immunity
human keratinocytes
immunomodulation
HLA-G1
PD-L1
TGFB1
Online Access:https://www.mdpi.com/2073-4409/10/6/1438
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spelling doaj-0088bc75cf794a57a53e15e7af34ecbf2021-06-30T23:38:52ZengMDPI AGCells2073-44092021-06-01101438143810.3390/cells10061438Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune CheckpointsGuillaume Mestrallet0Frédéric Auvré1Chantal Schenowitz2Edgardo D. Carosella3Joel LeMaoult4Michèle T. Martin5Nathalie Rouas-Freiss6Nicolas O. Fortunel7CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, FranceCEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, FranceCEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, FranceCEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, FranceCEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, FranceCEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, FranceCEA, DRF, Francois Jacob Institute of Biology, Hemato-Immunology Research Department, Saint-Louis Hospital, 75010 Paris, FranceCEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, FranceHuman 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<sup>+</sup> 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.https://www.mdpi.com/2073-4409/10/6/1438skin immunityhuman keratinocytesimmunomodulationHLA-G1PD-L1TGFB1
collection DOAJ
language English
format Article
sources DOAJ
author Guillaume Mestrallet
Frédéric Auvré
Chantal Schenowitz
Edgardo D. Carosella
Joel LeMaoult
Michèle T. Martin
Nathalie Rouas-Freiss
Nicolas O. Fortunel
spellingShingle Guillaume Mestrallet
Frédéric Auvré
Chantal Schenowitz
Edgardo D. Carosella
Joel LeMaoult
Michèle T. Martin
Nathalie Rouas-Freiss
Nicolas O. Fortunel
Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
Cells
skin immunity
human keratinocytes
immunomodulation
HLA-G1
PD-L1
TGFB1
author_facet Guillaume Mestrallet
Frédéric Auvré
Chantal Schenowitz
Edgardo D. Carosella
Joel LeMaoult
Michèle T. Martin
Nathalie Rouas-Freiss
Nicolas O. Fortunel
author_sort Guillaume Mestrallet
title Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_short Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_full Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_fullStr Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_full_unstemmed Human Keratinocytes Inhibit CD4<sup>+</sup> T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_sort human keratinocytes inhibit cd4<sup>+</sup> t-cell proliferation through tgfb1 secretion and surface expression of hla-g1 and pd-l1 immune checkpoints
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2021-06-01
description 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<sup>+</sup> 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.
topic skin immunity
human keratinocytes
immunomodulation
HLA-G1
PD-L1
TGFB1
url https://www.mdpi.com/2073-4409/10/6/1438
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