GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord–infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2 as examples, we show how this information can be used to develop new strategies for the functional modulation of Th17 cells and activated endothelial cells. Taken together, single-cell GPCR expression analysis identifies functionally relevant subpopulations with specific GPCR repertoires and provides a basis for the development of new therapeutic strategies in immune disorders.
Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C. Kurschus, Stefan Offermanns, Nina Wettschureck
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Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling
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Distinct transcriptional signatures in purified circulating immune cells drive heterogeneity in disease location in IBD
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Scientific Reports | 2022 |
G-protein Coupled Receptor 34 Promotes Gliomagenesis by Inducing Proliferation and Malignant Phenotype via TGF-Beta/Smad Signaling Pathway
Cheng Y, Heng X, Feng F |
Technology in cancer research & treatment | 2022 |
The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells
Paley MA, Baker BJ, Dunham SR, Linskey N, Cantoni C, Lee K, Hassman LM, Laurent J, Roberson ED, Clifford DB, Yokoyama WM |
Journal of Neuroimmunology | 2022 |
Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
N Jaeger, R Gamini, M Cella, JL Schettini, M Bugatti, S Zhao, CV Rosadini, E Esaulova, BD Luccia, B Kinnett, W Vermi, MN Artyomov, TA Wynn, RJ Xavier, SA Jelinsky, M Colonna |
Nature Communications | 2021 |
G-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators
M Gurusamy, D Tischner, J Shao, S Klatt, S Zukunft, R Bonnavion, S Günther, K Siebenbrodt, RI Kestner, T Kuhlmann, I Fleming, S Offermanns, N Wettschureck |
Nature Communications | 2021 |
CD4+ T cells contribute to neurodegeneration in Lewy body dementia
Gate D, Tapp E, Leventhal O, Shahid M, Nonninger TJ, Yang AC, Strempfl K, Unger MS, Fehlmann T, Oh H, Channappa D, Henderson VW, Keller A, Aigner L, Galasko DR, Davis MM, Poston KL, Wyss-Coray T |
Science (New York, N.Y.) | 2021 |
GPCRomics: An Approach to Discover GPCR Drug Targets
PA Insel, K Sriram, MW Gorr, SZ Wiley, A Michkov, C Salmerón, AM Chinn |
Trends in Pharmacological Sciences | 2019 |
GPR34 in spinal microglia exacerbates neuropathic pain in mice
A Sayo, H Konishi, M Kobayashi, K Kano, H Kobayashi, H Hibi, J Aoki, H Kiyama |
Journal of Neuroinflammation | 2019 |
Combining Optical Approaches with Human Inducible Pluripotent Stem Cells in G Protein-Coupled Receptor Drug Screening and Development
K Bourque, J Jones-Tabah, N Mnasri, R Martin, T Hébert |
Biomolecules | 2018 |