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Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter

Th22 cells constitute a recently described CD4(+) T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production h...

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Autores principales: Lopez, Daniel V., Al-Jaberi, Fatima A.H., Damas, Nkerorema D., Weinert, Brian T., Pus, Urska, Torres-Rusillo, Sara, Woetmann, Anders, Ødum, Niels, Bonefeld, Charlotte M., Kongsbak-Wismann, Martin, Geisler, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366496/
https://www.ncbi.nlm.nih.gov/pubmed/34408754
http://dx.doi.org/10.3389/fimmu.2021.715059
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author Lopez, Daniel V.
Al-Jaberi, Fatima A.H.
Damas, Nkerorema D.
Weinert, Brian T.
Pus, Urska
Torres-Rusillo, Sara
Woetmann, Anders
Ødum, Niels
Bonefeld, Charlotte M.
Kongsbak-Wismann, Martin
Geisler, Carsten
author_facet Lopez, Daniel V.
Al-Jaberi, Fatima A.H.
Damas, Nkerorema D.
Weinert, Brian T.
Pus, Urska
Torres-Rusillo, Sara
Woetmann, Anders
Ødum, Niels
Bonefeld, Charlotte M.
Kongsbak-Wismann, Martin
Geisler, Carsten
author_sort Lopez, Daniel V.
collection PubMed
description Th22 cells constitute a recently described CD4(+) T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production has been associated to some inflammatory skin diseases such as atopic dermatitis and psoriasis. How IL-22 production is regulated in human T cells is not fully known. In the present study, we identified conditions to generate Th22 cells that do not co-produce IL-17 from naïve human CD4(+) T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D(3) (1,25(OH)(2)D(3)) regulates IL-22 production in these cells. By studying T cells with a mutated vitamin D receptor (VDR), we demonstrate that the 1,25(OH)(2)D(3)-induced inhibition of il22 gene transcription is dependent on the transcriptional activity of the VDR in the T cells. Finally, we identified a vitamin D response element (VDRE) in the il22 promoter and demonstrate that 1,25(OH)(2)D(3)-VDR directly inhibits IL-22 production via this repressive VDRE.
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spelling pubmed-83664962021-08-17 Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter Lopez, Daniel V. Al-Jaberi, Fatima A.H. Damas, Nkerorema D. Weinert, Brian T. Pus, Urska Torres-Rusillo, Sara Woetmann, Anders Ødum, Niels Bonefeld, Charlotte M. Kongsbak-Wismann, Martin Geisler, Carsten Front Immunol Immunology Th22 cells constitute a recently described CD4(+) T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production has been associated to some inflammatory skin diseases such as atopic dermatitis and psoriasis. How IL-22 production is regulated in human T cells is not fully known. In the present study, we identified conditions to generate Th22 cells that do not co-produce IL-17 from naïve human CD4(+) T cells. We show that in addition to the transcription factors AhR and RORγt, the active form of vitamin D(3) (1,25(OH)(2)D(3)) regulates IL-22 production in these cells. By studying T cells with a mutated vitamin D receptor (VDR), we demonstrate that the 1,25(OH)(2)D(3)-induced inhibition of il22 gene transcription is dependent on the transcriptional activity of the VDR in the T cells. Finally, we identified a vitamin D response element (VDRE) in the il22 promoter and demonstrate that 1,25(OH)(2)D(3)-VDR directly inhibits IL-22 production via this repressive VDRE. Frontiers Media S.A. 2021-08-02 /pmc/articles/PMC8366496/ /pubmed/34408754 http://dx.doi.org/10.3389/fimmu.2021.715059 Text en Copyright © 2021 Lopez, Al-Jaberi, Damas, Weinert, Pus, Torres-Rusillo, Woetmann, Ødum, Bonefeld, Kongsbak-Wismann and Geisler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lopez, Daniel V.
Al-Jaberi, Fatima A.H.
Damas, Nkerorema D.
Weinert, Brian T.
Pus, Urska
Torres-Rusillo, Sara
Woetmann, Anders
Ødum, Niels
Bonefeld, Charlotte M.
Kongsbak-Wismann, Martin
Geisler, Carsten
Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title_full Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title_fullStr Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title_full_unstemmed Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title_short Vitamin D Inhibits IL-22 Production Through a Repressive Vitamin D Response Element in the il22 Promoter
title_sort vitamin d inhibits il-22 production through a repressive vitamin d response element in the il22 promoter
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366496/
https://www.ncbi.nlm.nih.gov/pubmed/34408754
http://dx.doi.org/10.3389/fimmu.2021.715059
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