Publications by authors named "Sébastien Hannedouche"

5 Publications

  • Page 1 of 1

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

Sci Signal 2017 Sep 12;10(496). Epub 2017 Sep 12.

Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland.

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 and has some features similar to the CC family of chemokines. was found in some human and mouse epithelia exposed to the environment, such as the colon and skin. In humans, was also abundant in the cervix. In skin, was readily detected after immunologic challenge and in human disease, for example, in psoriatic lesions. Allotransplantation of skin from -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scisignal.aal0180DOI Listing
September 2017

Identification of the C3a receptor (C3AR1) as the target of the VGF-derived peptide TLQP-21 in rodent cells.

J Biol Chem 2013 Sep 12;288(38):27434-27443. Epub 2013 Aug 12.

From Novartis AG, Novartis Campus, CH-4056 Basel, Switzerland. Electronic address:

TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation, and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This study describes the use of a series of studies that show G protein-coupled receptor-mediated biological activity of TLQP-21 signaling in CHO-K1 cells. Unbiased genome-wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible G protein-coupled receptors bringing about this activity. Further experiments using a series of defined receptor antagonists and siRNAs led to the identification of complement C3a receptor-1 (C3AR1) as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signaling to pertussis toxin is consistent with the known signaling pathway of C3AR1. The binding of TLQP-21 to C3AR1 not only has effects on signaling but also modulates cellular functions, as TLQP-21 was shown to have a role in directing migration of mouse RAW264.7 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M113.497214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779738PMC
September 2013

Oxysterols direct immune cell migration via EBI2.

Nature 2011 Jul 27;475(7357):524-7. Epub 2011 Jul 27.

Euroscreen S.A., 6041 Gosselies, Belgium.

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature10280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297623PMC
July 2011

The fate of P2Y-related orphan receptors: GPR80/99 and GPR91 are receptors of dicarboxylic acids.

Purinergic Signal 2004 Dec;1(1):17-20

Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Brussels, Belgium.

Several orphan G protein-coupled receptors are structurally close to the family of P2Y nucleotide receptors: GPR80/99 and GPR91 are close to P2Y(1/2/4/6/11) receptors, whereas GPR87, H963 and GPR34 are close to P2Y(12/13/14). Over the years, several laboratories have attempted without success to identify the ligands of those receptors. In early 2004, two papers have been published: One claiming that GPR80/99 is an AMP receptor, called P2Y(15), and the other one showing that GPR80/99 is a receptor for alpha-ketoglutarate, while GPR91 is a succinate receptor. The accompanying paper by Qi et al. entirely supports that GPR80/99 is an alpha-ketoglutarate receptor and not an AMP receptor. The closeness of dicarboxylic acid and P2Y nucleotide receptors might be linked to the negative charges of both types of ligands and the involvement of conserved Arg residues in their neutralization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11302-004-5071-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096567PMC
December 2004

Glucosinolates from Cardaria draba.

Fitoterapia 2002 Apr;73(2):177-8

Laboratoire Pharmacophores Redox, Phytochimie et Radiobiologie, EA 3030, Faculté des Sciences Pharmaceutiques, Université Paul Sabatier. 35, chemin des Maraîchers, 31062 cedex 4, Toulouse, France.

A new glucosinolate salt, L-prolinium 4-(methylsulfinyl)butyl glucosinolate, was isolated from the flowering heads of Cardaria draba and characterized by current spectroscopic methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0367-326x(02)00010-2DOI Listing
April 2002