title: The lysophosphatidylserine receptor GPR174 constrains regulatory T cell development and function.
abstract: Regulatory T cell (T reg cell) numbers and activities are tightly calibrated to maintain immune homeostasis, but the mechanisms involved are incompletely defined. Here, we report that the lysophosphatidylserine (LysoPS) receptor GPR174 is abundantly expressed in developing and mature T reg cells. In mice that lacked this X-linked gene, T reg cell generation in the thymus was intrinsically favored, and a higher fraction of peripheral T reg cells expressed CD103. LysoPS could act in vitro via GPR174 to suppress T cell proliferation and T reg cell generation. In vivo, LysoPS was detected in lymphoid organ and spinal cord tissues and was abundant in the colon. Gpr174(-/Y) mice were less susceptible to experimental autoimmune encephalomyelitis than wild-type mice, and GPR174 deficiency in T reg cells contributed to this phenotype. This study provides evidence that a bioactive lipid, LysoPS, negatively influences T reg cell accumulation and activity through GPR174. As such, GPR174 antagonists might have therapeutic potential for promoting immune regulation in the context of autoimmune disease.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Barnes
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Jinping
authors.initials: J
authors.lastname: An
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143 Jason.Cyster@ucsf.edu.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D003106:Colon / Q000378:metabolism; D017931:DNA Primers; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000276:immunology* / Q000378:metabolism; D049312:Receptors, Lysophospholipid / Q000276:immunology* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; C000601090:GPR174 protein, mouse; D039001:Integrin alpha Chains; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C091367:alpha E integrins; C025059:lysophosphatidylserine