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Publication : A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia.

First Author  Suply T Year  2017
Journal  Sci Signal Volume  10
Issue  496 PubMed ID  28900043
Mgi Jnum  J:248456 Mgi Id  MGI:6094556
Doi  10.1126/scisignal.aal0180 Citation  Suply T, et al. (2017) A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia. Sci Signal 10(496)
abstractText  GPR15 is an orphan G protein-coupled receptor (GPCR) that is found in lymphocytes. It functions as a co-receptor of simian immunodeficiency virus and HIV-2 and plays a role in the trafficking of T cells to the lamina propria in the colon and to the skin. We describe the purification from porcine colonic tissue extracts of an agonistic ligand for GPR15 and its functional characterization. In humans, this ligand, which we named GPR15L, is encoded by the gene C10ORF99 and has some features similar to the CC family of chemokines. GPR15L was found in some human and mouse epithelia exposed to the environment, such as the colon and skin. In humans, GPR15L was also abundant in the cervix. In skin, GPR15L was readily detected after immunologic challenge and in human disease, for example, in psoriatic lesions. Allotransplantation of skin from Gpr15l-deficient mice onto wild-type mice resulted in substantial graft protection, suggesting nonredundant roles for GPR15 and GPR15L in the generation of effector T cell responses. Together, these data identify a receptor-ligand pair that is required for immune homeostasis at epithelia and whose modulation may represent an alternative approach to treating conditions affecting the skin such as psoriasis.
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