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RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells

Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid recepto...

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Autores principales: Hashimoto-Hill, Seika, Friesen, Leon, Park, Sungtae, Im, Suji, Kaplan, Mark H., Kim, Chang H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156335/
https://www.ncbi.nlm.nih.gov/pubmed/30254197
http://dx.doi.org/10.1038/s41467-018-06341-8
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author Hashimoto-Hill, Seika
Friesen, Leon
Park, Sungtae
Im, Suji
Kaplan, Mark H.
Kim, Chang H.
author_facet Hashimoto-Hill, Seika
Friesen, Leon
Park, Sungtae
Im, Suji
Kaplan, Mark H.
Kim, Chang H.
author_sort Hashimoto-Hill, Seika
collection PubMed
description Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin(+ )conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPβ. RARα promotes the development of LCs and langerin(+) conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.
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spelling pubmed-61563352018-09-27 RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells Hashimoto-Hill, Seika Friesen, Leon Park, Sungtae Im, Suji Kaplan, Mark H. Kim, Chang H. Nat Commun Article Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin(+ )conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPβ. RARα promotes the development of LCs and langerin(+) conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations. Nature Publishing Group UK 2018-09-25 /pmc/articles/PMC6156335/ /pubmed/30254197 http://dx.doi.org/10.1038/s41467-018-06341-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hashimoto-Hill, Seika
Friesen, Leon
Park, Sungtae
Im, Suji
Kaplan, Mark H.
Kim, Chang H.
RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title_full RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title_fullStr RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title_full_unstemmed RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title_short RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
title_sort rarα supports the development of langerhans cells and langerin-expressing conventional dendritic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156335/
https://www.ncbi.nlm.nih.gov/pubmed/30254197
http://dx.doi.org/10.1038/s41467-018-06341-8
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