Research ArticleImmunology

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

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Sci. Signal.  12 Sep 2017:
Vol. 10, Issue 496, eaal0180
DOI: 10.1126/scisignal.aal0180

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Deorphanizing a chemoattractant receptor

The orphan G protein–coupled receptor GPR15 mediates the trafficking of lymphocytes to the colon and the skin and the recruitment of effector T cells to inflamed intestinal tissue. Suply et al. purified a natural ligand of GPR15 (GPR15L) from porcine colonic extracts. In vitro assays showed that GPR15L specifically activated GPR15, but not other chemoattractant receptors. Although migration assays suggested that GPR15L inhibited chemokine-induced T cell migration, mouse skin allotransplantations showed that GPR15L recruited CD8+ T cells to the graft and that loss of the ligand was associated with increased graft protection. Given that GPR15L mRNA is abundant in psoriatic lesions, these data suggest that targeting the GPR15-GPR15L axis may help in the treatment of inflammatory skin conditions.