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Title: Ezh2 controls skin tolerance through distinct mechanisms in different subsets of skin dendritic cells
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
Keywords: Dermatology
Science::Biological sciences
Issue Date: 2018
Source: 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
Series/Report no.: iScience
Abstract: 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.
DOI: 10.1016/j.isci.2018.11.019
Rights: © 2018 The Authors.This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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