2. Academic Validation
  3. A natural ligand for the orphan receptor GPR15 modulates lymphocyte recruitment to epithelia

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

  • Sci Signal. 2017 Sep 12;10(496):eaal0180. doi: 10.1126/scisignal.aal0180.
Thomas Suply 1,  Sébastien Hannedouche 2,  Nathalie Carte 1,  Jianping Li 1,  Bianka Grosshans 1,  Michael Schaefer 1,  Layla Raad 1,  Valérie Beck 1,  Solange Vidal 1,  Agnès Hiou-Feige 1,  Noémie Beluch 1,  Samuel Barbieri 1,  Johann Wirsching 1,  Nadine Lageyre 1,  Frank Hillger 1,  Corinne Debon 1,  Janet Dawson 1,  Philip Smith 1,  Vincent Lannoy 2,  Michel Detheux 2,  Francis Bitsch 1,  Rocco Falchetto 1,  Tewis Bouwmeester 1,  Jeffrey Porter 3,  Birgit Baumgarten 1,  Keith Mansfield 3,  José M Carballido 1,  Klaus Seuwen 4,  Frédéric Bassilana 4
Affiliations

Affiliations

  • 1 Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland.
  • 2 Ogeda SA, 6041 Gosselies, Belgium.
  • 3 Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • 4 Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland. frederic.bassilana@novartis.com klaus.seuwen@novartis.com.
PMID: 28900043 DOI: 10.1126/scisignal.aal0180
Abstract

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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