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Ezh2 Controls Skin Tolerance through Distinct Mechanisms in Different Subsets of Skin Dendritic Cells.

iScience (2018-11-30)
Jia Tong Loh, Thomas Jun Feng Lim, Kyoko Ikumi, Takuma Matoba, Baptiste Janela, Merry Gunawan, Tatsuya Toyama, Maegan Bunjamin, Lai Guan Ng, Michael Poidinger, Akimichi Morita, Florent Ginhoux, Sayuri Yamazaki, Kong-Peng Lam, I-Hsin Su
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.

MATERIALS
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Product Description

Sigma-Aldrich
Monoclonal Anti-Talin antibody produced in mouse, clone 8d4, ascites fluid