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

Gurusamy, Malarvizhi; Tischner, Denise; Shao, Jingchen; Klatt, Stephan; Zukunft, Sven; Bonnavion, Rémy; Günther, Stefan; Siebenbrodt, Kai; Kestner, Roxane-Isabelle; Fleming, Ingrid; Offermanns, Stefan; Wettschureck, Nina

doi:10.1038/s41467-021-26882-9

Cited by 30 publications

(22 citation statements)

References 75 publications

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“…A surprising observation in our work was that GPR174-dependent CD86 induction was unaffected by the addition of lysoPS to the cultures. However, lymphocytes can generate lysoPS ( 8 , 57 , 58 ) and our findings indicate that lysoPS abundance in B cells increases within minutes of in vitro incubation. We speculate that the lack of activity of exogenously added lysoPS reflects efficient occupancy of the receptor by lysoPS in an autocrine manner.…”

Section: Discussionmentioning

confidence: 57%

GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells

Wolf

Howard

Duan

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceModeling immune responses in vitro is critical for studying many facets of the B cell response. We show that during culture without stimulation, mouse B cells undergo massive changes in gene expression. Many of these changes are promoted by GPR174 signaling via Gαs. GPR174 and Gαs also contribute to reduced B cell viability during culture. We suggest that GPR174 antagonists may be useful to reduce the shift in gene expression and to augment B cell survival during culture. We also provide evidence that ligand engagement of GPR174 can activate this pathway in vivo. Variants in the GPR174 locus have been associated with autoimmune diseases. Our findings provide knowledge for understanding how alterations in GPR174 expression may contribute to disease.

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Section: Discussionmentioning

confidence: 57%

GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells

Wolf

Howard

Duan

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…P2RY10 (P2Y Receptor Family Member 10) was also a G-protein-coupled receptor. P2RY10 could facilitate chemokine-induced CD4 + T cell migration and was potentially involved in the immune response ( Gurusamy et al, 2021 ). FLT3LG (Fms Related Receptor Tyrosine Kinase 3 Ligand) combined with FLT3 on dendritic cells to stimulate their differentiation and proliferation.…”

Section: Discussionmentioning

confidence: 99%

Immune Infiltration Characteristics and a Gene Prognostic Signature Associated With the Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Zhu

Yang

et al. 2022

Front. Genet.

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Background: Immunotherapy has become the new standard of care for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and PD-L1 is a widely used biomarker for immunotherapeutic response. However, PD-L1 expression in most cancer patients is low, and alternative biomarkers used to screen the population benefiting from immunotherapy are still being explored. Tumor microenvironment (TME), especially tumor immune-infiltrating cells, regulates the body’s immunity, affects the tumor growth, and is expected to be a promising biomarker for immunotherapy.Purpose: This article mainly discussed how the immune-infiltrating cell patterns impacted immunity, thereby affecting HNSCC patients’ prognosis.Method: The immune-infiltrating cell profile was generated by the CIBERSORT algorithm based on the transcriptomic data of HNSCC. Consensus clustering was used to divide groups with different immune cell infiltration patterns. Differentially expressed genes (DEGs) obtained from the high and low immune cell infiltration (ICI) groups were subjected to Kaplan–Meier and univariate Cox analysis. Significant prognosis-related DEGs were involved in the construction of a prognostic signature using multivariate Cox analysis.Results: In our study, 408 DEGs were obtained from high- and low-ICI groups, and 59 of them were significantly associated with overall survival (OS). Stepwise multivariate Cox analysis developed a 16-gene prognostic signature, which could distinguish favorable and poor prognosis of HNSCC patients. An ROC curve and nomogram verified the sensitivity and accuracy of the prognostic signature. The AUC values for 1 year, 2 years, and 3 years were 0.712, 0.703, and 0.700, respectively. TCGA-HNSCC cohort, GSE65858 cohort, and an independent GSE41613 cohort proved a similar prognostic significance. Notably, the prognostic signature distinguished the expression of promising immune inhibitory receptors (IRs) well and could predict the response to immunotherapy.Conclusion: We established a tumor immune cell infiltration (TICI)-based 16-gene signature, which could distinguish patients with different prognosis and help predict the response to immunotherapy.

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“…LPS suppresses the activation of T lymphocytes through GPR174, 12 while LPS facilitates the migration of CD4 T cells through P2Y10. 13 LPI and LPG act on GPR55, and this axis has been considered as a pro-inflammatory pathway. 14 LPI and LPG are produced from phosphatidylinositol (PI) and phosphatidylglycerol (PG), respectively.…”

Section: Introductionmentioning

confidence: 99%

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Kurano

Okamoto

Jubishi

et al. 2022

Clinical & Translational Med

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Background A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID‐19). Therefore, investigating biomarkers associated with disease severity is important for understanding the mechanisms responsible for this heterogeneity and for developing novel agents to prevent critical conditions. This study aimed to elucidate the modulations of sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties. Methods We measured the serum sphingolipid and glycerophospholipid levels in a total of 887 samples from 215 COVID‐19 subjects, plus 115 control subjects without infectious diseases and 109 subjects with infectious diseases other than COVID‐19. Results We observed the dynamic modulations of sphingolipids and glycerophospholipids in the serum of COVID‐19 subjects, depending on the time course and severity. The elevation of C16:0 ceramide and lysophosphatidylinositol and decreases in C18:1 ceramide, dihydrosphingosine, lysophosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol were specific to COVID‐19. Regarding the association with maximum severity, phosphatidylinositol and phosphatidylcholine species with long unsaturated acyl chains were negatively associated, while lysophosphatidylethanolamine and phosphatidylethanolamine were positively associated with maximum severity during the early phase. Lysophosphatidylcholine and phosphatidylcholine had strong negative correlations with CRP, while phosphatidylethanolamine had strong positive ones. C16:0 ceramide, lysophosphatidylcholine, phosphatidylcholine and phosphatidylethanolamine species with long unsaturated acyl chains had negative correlations with D‐dimer, while phosphatidylethanolamine species with short acyl chains and phosphatidylinositol had positive ones. Several species of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin might serve as better biomarkers for predicting severe COVID‐19 during the early phase than CRP and D‐dimer. Compared with the lipid modulations seen in mice treated with lipopolysaccharide, tissue factor, or histone, the lipid modulations observed in severe COVID‐19 were most akin to those in mice administered lipopolysaccharide. Conclusion A better understanding of the disturbances in sphingolipids and glycerophospholipids observed in this study will prompt further investigation to develop laboratory testing for predicting maximum severity and/or novel agents to suppress the aggravation of COVID‐19.

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

Cited by 30 publications

References 75 publications

GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells

GPR174 signals via Gαs to control a CD86-containing gene expression program in B cells

Immune Infiltration Characteristics and a Gene Prognostic Signature Associated With the Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

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