GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses
G-protein coupled receptors (GPCR) regulate 3’,5’-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Se...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1113348/full |
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| author | Paula F. Krieg Jana K. Sonner Roberta Kurelic Jan Broder Engler Marlena F. Scharenberg Simone Bauer Viacheslav O. Nikolaev Manuel A. Friese |
| author_facet | Paula F. Krieg Jana K. Sonner Roberta Kurelic Jan Broder Engler Marlena F. Scharenberg Simone Bauer Viacheslav O. Nikolaev Manuel A. Friese |
| author_sort | Paula F. Krieg |
| collection | DOAJ |
| description | G-protein coupled receptors (GPCR) regulate 3’,5’-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Several GPCRs have been identified to be crucial for Teff and Treg function. However, the role of the orphan, constitutively active Gs-coupled GPCR GPR52 is unknown. Here we show that GPR52 regulates cAMP levels in T cells but does not affect T cell function. We found that stimulation of transfected HEK cells or primary T cells with a GPR52 agonist results in a rise of intracellular cAMP. However, neither Gpr52 deficiency nor pharmacological modulation of GPR52 by antagonists or agonists affected T cell activation, differentiation, and proliferation or Treg-mediated immunosuppression. Moreover, Gpr52 deletion did not modify the clinical disease course of experimental autoimmune encephalomyelitis (EAE). Our results demonstrate that a modulation of cAMP levels in T cells does not inevitably result in altered T cell function. While we could not identify an obvious role of GPR52 in in vitro T cell assays and in vivo CNS autoimmunity, it might regulate T cell function in a different context or affect the function of other GPR52-expressing cells. |
| first_indexed | 2024-04-10T20:47:13Z |
| format | Article |
| id | doaj.art-af0a257409994883bba763b26456c0a5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:47:13Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-af0a257409994883bba763b26456c0a52023-01-24T06:27:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.11133481113348GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responsesPaula F. Krieg0Jana K. Sonner1Roberta Kurelic2Jan Broder Engler3Marlena F. Scharenberg4Simone Bauer5Viacheslav O. Nikolaev6Manuel A. Friese7Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyG-protein coupled receptors (GPCR) regulate 3’,5’-cyclic adenosine monophosphate (cAMP) levels in T cells. cAMP as ubiquitous second messenger is crucial for adequate physiology of T cells by mediating effector T cell (Teff) function as well as regulatory T cell (Treg)-mediated immunosuppression. Several GPCRs have been identified to be crucial for Teff and Treg function. However, the role of the orphan, constitutively active Gs-coupled GPCR GPR52 is unknown. Here we show that GPR52 regulates cAMP levels in T cells but does not affect T cell function. We found that stimulation of transfected HEK cells or primary T cells with a GPR52 agonist results in a rise of intracellular cAMP. However, neither Gpr52 deficiency nor pharmacological modulation of GPR52 by antagonists or agonists affected T cell activation, differentiation, and proliferation or Treg-mediated immunosuppression. Moreover, Gpr52 deletion did not modify the clinical disease course of experimental autoimmune encephalomyelitis (EAE). Our results demonstrate that a modulation of cAMP levels in T cells does not inevitably result in altered T cell function. While we could not identify an obvious role of GPR52 in in vitro T cell assays and in vivo CNS autoimmunity, it might regulate T cell function in a different context or affect the function of other GPR52-expressing cells.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1113348/fullcAMPexperimental autoimmune encephalomyelitisFRETGPCRmultiple sclerosisT cells |
| spellingShingle | Paula F. Krieg Jana K. Sonner Roberta Kurelic Jan Broder Engler Marlena F. Scharenberg Simone Bauer Viacheslav O. Nikolaev Manuel A. Friese GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses Frontiers in Immunology cAMP experimental autoimmune encephalomyelitis FRET GPCR multiple sclerosis T cells |
| title | GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses |
| title_full | GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses |
| title_fullStr | GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses |
| title_full_unstemmed | GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses |
| title_short | GPR52 regulates cAMP in T cells but is dispensable for encephalitogenic responses |
| title_sort | gpr52 regulates camp in t cells but is dispensable for encephalitogenic responses |
| topic | cAMP experimental autoimmune encephalomyelitis FRET GPCR multiple sclerosis T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1113348/full |
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