Orphan chemoattractant receptor GPR15 mediates dendritic epidermal T-cell recruitment to the skin.
Homing of murine dendritic epidermal T cells (DETCs) from the thymus to the skin is regulated by specific trafficking receptors during late embryogenesis. Once in the epidermis, Vγ3δ1 TCR DETCs are maintained through self-renewal and participate in wound healing. GPR15 is an orphan G protein-linked chemoattractant receptor involved in the recruitment of regulatory T cells to the colon. Here we show that GPR15 is highly expressed on fetal thymic DETC precursors and on recently recruited DETCs, and mediates the earliest seeding of the epidermis, which occurs at the time of establishment of skin barrier function. DETCs in GPR15(-/-) mice remain low at birth, but later participation of CCR10 and CCR4 in DETC homing allows DETCs to reach near normal levels in adult skin. Our findings establish a role for GPR15 in skin lymphocyte homing and suggest that it may contribute to lymphocyte subset targeting to diverse epithelial sites.
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Katharina
K
Lahl
Johanna
J
Sweere
Junliang
J
Pan
Eugene
E
Butcher
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
C515355:Ccr4 protein, mouse; C523001:Gpr15 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054398:Receptors, CCR4; D043562:Receptors, G-Protein-Coupled
Cell homing; Cell surface molecules; Chemokines · DETC; GPR15; Skin diseases/immunology; Skin homing; Trafficking receptor; g/d T cells