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  G-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators

Gurusamy, M., Tischner, D., Shao, J., Klatt, S., Zukunft, S., Bonnavion, R., et al. (2021). G-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators. NATURE COMMUNICATIONS, 12(1): 6798. doi:10.1038/s41467-021-26882-9.

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Gurusamy, Malarvizhi1, Author              
Tischner, Denise1, Author              
Shao, Jingchen1, Author              
Klatt, Stephan, Author
Zukunft, Sven, Author
Bonnavion, Remy1, Author              
Guenther, Stefan2, Author              
Siebenbrodt, Kai, Author
Kestner, Roxane-Isabelle, Author
Kuhlmann, Tanja, Author
Fleming, Ingrid, Author
Offermanns, Stefan1, Author              
Wettschureck, Nina1, Author              
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              
2Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 Abstract: G-protein-coupled receptors (GPCRs), especially chemokine receptors, play a central role in the regulation of T cell migration. Various GPCRs are upregulated in activated CD4 T cells, including P2Y10, a putative lysophospholipid receptor that is officially still considered an orphan GPCR, i.e., a receptor with unknown endogenous ligand. Here we show that in mice lacking P2Y10 in the CD4 T cell compartment, the severity of experimental autoimmune encephalomyelitis and cutaneous contact hypersensitivity is reduced. P2Y10-deficient CD4 T cells show normal activation, proliferation and differentiation, but reduced chemokine-induced migration, polarization, and RhoA activation upon in vitro stimulation. Mechanistically, CD4 T cells release the putative P2Y10 ligands lysophosphatidylserine and ATP upon chemokine exposure, and these mediators induce P2Y10-dependent RhoA activation in an autocrine/paracrine fashion. ATP degradation impairs RhoA activation and migration in control CD4 T cells, but not in P2Y10-deficient CD4 T cells. Importantly, the P2Y10 pathway appears to be conserved in human T cells. Taken together, P2Y10 mediates RhoA activation in CD4 T cells in response to auto-/paracrine-acting mediators such as LysoPS and ATP, thereby facilitating chemokine-induced migration and, consecutively, T cell-mediated diseases. P2Y10 is a G-protein-coupled receptor that is expressed in CD4 T cells. Here authors show that its ligands, lysophosphatidylserine and ATP, are induced in T cells upon chemokine stimulation and regulate RhoA activation and migration through an autocrine/paracrine loop.

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 Dates: 2021-11-23
 Publication Status: Published online
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 Identifiers: ISI: 000723149100022
DOI: 10.1038/s41467-021-26882-9
PMID: 34815397
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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Pages: - Volume / Issue: 12 (1) Sequence Number: 6798 Start / End Page: - Identifier: -