Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells

Ezh2, a well-established epigenetic repressor, can down-regulate leukocyte inflammatory responses, but its role in cutaneous health remains elusive. Here we demonstrate that Ezh2 controls cutaneous tolerance by regulating Langerhans cell (LC) transmigration across the epidermal basement membrane dir...

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Main Authors: Morita, Akimichi, Ginhoux, Florent, Loh, Jia Tong, Lim, Thomas Jun Feng, Ikumi, Kyoko, Matoba, Takuma, Janela, Baptiste, Gunawan, Merry, Toyama, Tatsuya, Bunjamin, Maegan, Ng, Lai Guan, Poidinger, Michael, Yamazaki, Sayuri, Lam, Kong-Peng, Su, I-hsin
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/85704
http://hdl.handle.net/10220/49842
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-857042023-02-28T17:07:06Z Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells Morita, Akimichi Ginhoux, Florent Loh, Jia Tong Lim, Thomas Jun Feng Ikumi, Kyoko Matoba, Takuma Janela, Baptiste Gunawan, Merry Toyama, Tatsuya Bunjamin, Maegan Ng, Lai Guan Poidinger, Michael Yamazaki, Sayuri Lam, Kong-Peng Su, I-hsin School of Biological Sciences Dermatology Immunology Science::Biological sciences Ezh2, a well-established epigenetic repressor, can down-regulate leukocyte inflammatory responses, but its role in cutaneous health remains elusive. Here we demonstrate that Ezh2 controls cutaneous tolerance by regulating Langerhans cell (LC) transmigration across the epidermal basement membrane directly via Talin1 methylation. Ezh2 deficiency impaired disassembly of adhesion structures in LCs, leading to their defective integrin-dependent emigration from the epidermis and failure in tolerance induction. Moreover, mobilization of Ezh2-deficient Langerin– dermal dendritic cells (dDCs) via high-dose treatment with a weak allergen restored tolerance, which is associated with an increased tolerogenic potential of Langerin– dDCs likely due to epigenetic de-repression of Aldh in the absence of Ezh2. Our data reveal novel roles for Ezh2 in governing LC- and dDC-mediated host protection against cutaneous allergen via distinct mechanisms. Published version 2019-09-03T03:21:19Z 2019-12-06T16:08:40Z 2019-09-03T03:21:19Z 2019-12-06T16:08:40Z 2018 Journal Article Loh, J. T., Lim, T. J. F., Ikumi, K., Matoba, T., Janela, B., Gunawan, M., . . . Su, I.-h. (2018). Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells. iScience, 10, 23-39. doi:10.1016/j.isci.2018.11.019 https://hdl.handle.net/10356/85704 http://hdl.handle.net/10220/49842 10.1016/j.isci.2018.11.019 en iScience 10.21979/N9/7L5A0F © 2018 The Authors.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 36 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Dermatology
Immunology
Science::Biological sciences
spellingShingle Dermatology
Immunology
Science::Biological sciences
Morita, Akimichi
Ginhoux, Florent
Loh, Jia Tong
Lim, Thomas Jun Feng
Ikumi, Kyoko
Matoba, Takuma
Janela, Baptiste
Gunawan, Merry
Toyama, Tatsuya
Bunjamin, Maegan
Ng, Lai Guan
Poidinger, Michael
Yamazaki, Sayuri
Lam, Kong-Peng
Su, I-hsin
Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
description Ezh2, a well-established epigenetic repressor, can down-regulate leukocyte inflammatory responses, but its role in cutaneous health remains elusive. Here we demonstrate that Ezh2 controls cutaneous tolerance by regulating Langerhans cell (LC) transmigration across the epidermal basement membrane directly via Talin1 methylation. Ezh2 deficiency impaired disassembly of adhesion structures in LCs, leading to their defective integrin-dependent emigration from the epidermis and failure in tolerance induction. Moreover, mobilization of Ezh2-deficient Langerin– dermal dendritic cells (dDCs) via high-dose treatment with a weak allergen restored tolerance, which is associated with an increased tolerogenic potential of Langerin– dDCs likely due to epigenetic de-repression of Aldh in the absence of Ezh2. Our data reveal novel roles for Ezh2 in governing LC- and dDC-mediated host protection against cutaneous allergen via distinct mechanisms.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Morita, Akimichi
Ginhoux, Florent
Loh, Jia Tong
Lim, Thomas Jun Feng
Ikumi, Kyoko
Matoba, Takuma
Janela, Baptiste
Gunawan, Merry
Toyama, Tatsuya
Bunjamin, Maegan
Ng, Lai Guan
Poidinger, Michael
Yamazaki, Sayuri
Lam, Kong-Peng
Su, I-hsin
format Article
author Morita, Akimichi
Ginhoux, Florent
Loh, Jia Tong
Lim, Thomas Jun Feng
Ikumi, Kyoko
Matoba, Takuma
Janela, Baptiste
Gunawan, Merry
Toyama, Tatsuya
Bunjamin, Maegan
Ng, Lai Guan
Poidinger, Michael
Yamazaki, Sayuri
Lam, Kong-Peng
Su, I-hsin
author_sort Morita, Akimichi
title Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
title_short Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
title_full Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
title_fullStr Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
title_full_unstemmed Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
title_sort ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
publishDate 2019
url https://hdl.handle.net/10356/85704
http://hdl.handle.net/10220/49842
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