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Human Keratinocytes Inhibit CD4(+) 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(+) T-cell proliferation under both normal and inflammatory conditi...

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Autores principales: Mestrallet, Guillaume, Auvré, Frédéric, Schenowitz, Chantal, Carosella, Edgardo D., LeMaoult, Joel, Martin, Michèle T., Rouas-Freiss, Nathalie, Fortunel, Nicolas O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227977/
https://www.ncbi.nlm.nih.gov/pubmed/34201301
http://dx.doi.org/10.3390/cells10061438
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author Mestrallet, Guillaume
Auvré, Frédéric
Schenowitz, Chantal
Carosella, Edgardo D.
LeMaoult, Joel
Martin, Michèle T.
Rouas-Freiss, Nathalie
Fortunel, Nicolas O.
author_facet Mestrallet, Guillaume
Auvré, Frédéric
Schenowitz, Chantal
Carosella, Edgardo D.
LeMaoult, Joel
Martin, Michèle T.
Rouas-Freiss, Nathalie
Fortunel, Nicolas O.
author_sort Mestrallet, Guillaume
collection PubMed
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(+) 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.
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spelling pubmed-82279772021-06-26 Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints Mestrallet, Guillaume Auvré, Frédéric Schenowitz, Chantal Carosella, Edgardo D. LeMaoult, Joel Martin, Michèle T. Rouas-Freiss, Nathalie Fortunel, Nicolas O. Cells Article 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. MDPI 2021-06-08 /pmc/articles/PMC8227977/ /pubmed/34201301 http://dx.doi.org/10.3390/cells10061438 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mestrallet, Guillaume
Auvré, Frédéric
Schenowitz, Chantal
Carosella, Edgardo D.
LeMaoult, Joel
Martin, Michèle T.
Rouas-Freiss, Nathalie
Fortunel, Nicolas O.
Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_full Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_fullStr Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_full_unstemmed Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_short Human Keratinocytes Inhibit CD4(+) T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and PD-L1 Immune Checkpoints
title_sort human keratinocytes inhibit cd4(+) t-cell proliferation through tgfb1 secretion and surface expression of hla-g1 and pd-l1 immune checkpoints
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227977/
https://www.ncbi.nlm.nih.gov/pubmed/34201301
http://dx.doi.org/10.3390/cells10061438
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