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

Author

Listed:
  • Malarvizhi Gurusamy

    (Max Planck Institute for Heart and Lung Research)

  • Denise Tischner

    (Max Planck Institute for Heart and Lung Research)

  • Jingchen Shao

    (Max Planck Institute for Heart and Lung Research)

  • Stephan Klatt

    (Goethe University)

  • Sven Zukunft

    (Goethe University)

  • Remy Bonnavion

    (Max Planck Institute for Heart and Lung Research)

  • Stefan Günther

    (Max Planck Institute for Heart and Lung Research)

  • Kai Siebenbrodt

    (University of Frankfurt)

  • Roxane-Isabelle Kestner

    (University of Frankfurt)

  • Tanja Kuhlmann

    (University of Münster)

  • Ingrid Fleming

    (Goethe University)

  • Stefan Offermanns

    (Max Planck Institute for Heart and Lung Research
    Goethe University Frankfurt)

  • Nina Wettschureck

    (Max Planck Institute for Heart and Lung Research
    Goethe University Frankfurt)

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.

Suggested Citation

  • Malarvizhi Gurusamy & Denise Tischner & Jingchen Shao & Stephan Klatt & Sven Zukunft & Remy Bonnavion & Stefan Günther & Kai Siebenbrodt & Roxane-Isabelle Kestner & Tanja Kuhlmann & Ingrid Fleming & S, 2021. "G-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26882-9
    DOI: 10.1038/s41467-021-26882-9
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    References listed on IDEAS

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    1. Kushal K Dey & Chiaowen Joyce Hsiao & Matthew Stephens, 2017. "Visualizing the structure of RNA-seq expression data using grade of membership models," PLOS Genetics, Public Library of Science, vol. 13(3), pages 1-23, March.
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