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Epidermis instructs skin homing receptor expression in human T cells.

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.

journal_name

Blood

journal_title

Blood

authors

McCully ML,Ladell K,Hakobyan S,Mansel RE,Price DA,Moser B

doi

10.1182/blood-2012-05-433037

subject

Has Abstract

pub_date

2012-11-29 00:00:00

pages

4591-8

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2012-05-433037

journal_volume

120

pub_type

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