Skin metabolites define a new paradigm in the localization of skin tropic memory T cells

McCully, Michelle L., Collins, Paul J., Hughes, Timothy R. ORCID: https://orcid.org/0000-0003-2348-3490, Thomas, Christopher P. ORCID: https://orcid.org/0000-0001-5840-8613, Billen, Jaak, O'Donnell, Valerie B. ORCID: https://orcid.org/0000-0003-4089-8460 and Moser, Bernhard ORCID: https://orcid.org/0000-0002-4354-4572 2015. Skin metabolites define a new paradigm in the localization of skin tropic memory T cells. Journal of Immunology 195 (1) , pp. 96-104. 10.4049/jimmunol.1402961

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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. The expression of CCR8 during naive T cell activation is controlled by skin-specific factors derived from epidermal keratinocytes and not by resident dendritic cells. In this study, we show that the CCR8-inducing factors are heat stable and protease resistant and include the vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 and PGE2. The effect of either metabolite alone on CCR8 expression was weak, whereas their combination resulted in robust CCR8 expression. Elevation of intracellular cAMP was essential because PGE2 could be substituted with the adenylyl cyclase agonist forskolin, and CCR8 expression was sensitive to protein kinase A inhibition. For effective induction, exposure of naive T cells to these epidermal factors needed to occur either prior to or during T cell activation even though CCR8 was only detected 4–5 d later in proliferating T cells. The importance of tissue environments in maintaining cellular immune surveillance networks within distinct healthy tissues provides a paradigm shift in adaptive immunity. Epidermal-derived vitamin D3 metabolites and PGs provide an essential cue for the localization of CCR8+ immune surveillance T cells within healthy human skin.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	1 May 2015
Last Modified:	15 Mar 2024 07:23
URI:	https://orca.cardiff.ac.uk/id/eprint/74083

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