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Epidermis instructs skin homing receptor expression in human T cells

McCully, Michelle L., Ladell, Kristin Ingrid, Hakobyan, Svetlana, Mansel, Robert Edward, Price, David and Moser, Bernhard 2012. Epidermis instructs skin homing receptor expression in human T cells. Blood 120 (23) , pp. 4591-4598. 10.1182/blood-2012-05-433037

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Abstract

The localization of memory T cells to human skin is essential for long-term immune surveillance and the maintenance of barrier integrity. Although the mechanisms controlling memory T-cell migration to peripheral tissues are poorly understood, the current paradigm includes the localized secretion of “imprinting” signals from tissue-resident dendritic cells in the draining lymph nodes. Here we show that CCR8 expression by newly activated naive T cells is regulated by skin-specific factor(s) derived primarily from epidermal keratinocytes, thereby providing a mechanism for the preferential expression of CCR8 by skin-resident memory T cells. Importantly, no such effects were observed after coculture with primary cells from skin-unrelated epithelia, including mesothelium and small intestine. The keratinocyte-derived CCR8-inducing factor(s) were soluble, and independent of vitamins A and D. Furthermore, the induction of CCR8 under these conditions correlated with an increase in cutaneous lymphocyte-associated antigen expression. Our findings challenge current tissue homing paradigms, especially those involving CCR10, and emphasize the importance of steady-state epidermis rather than tissue-resident dendritic cells in controlling the localization of memory T cells within human skin.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RL Dermatology
Publisher: American Society of Hematology
ISSN: 0006-4971
Last Modified: 13 Nov 2017 23:54
URI: http://orca.cf.ac.uk/id/eprint/42807

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