Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin

Brian J. Laidlaw, Elizabeth E. Gray, Yang Zhang, Francisco Ramírez-Valle, Jason G. Cyster

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Maintenance of a population of IL-17–committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17+ γδ T cells establish residence within the dermis and identify a role for S1PR2 in restraining the egress of tissue-resident lymphocytes.

Original languageEnglish
Pages (from-to)1487-1496
Number of pages10
JournalJournal of Experimental Medicine
Volume216
Issue number7
DOIs
StatePublished - Jul 1 2019

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