title: RGS10 deficiency ameliorates the severity of disease in experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  Regulator of G-protein signaling (RGS) family proteins, which are GTPase accelerating proteins (GAPs) that negatively regulate G-protein-coupled receptors (GPCRs), are known to be important modulators of immune cell activation and function. Various single-nucleotide polymorphisms in RGS proteins highly correlate with increased risk for multiple sclerosis (MS), an autoimmune, neurodegenerative disorder. An in-depth search of the gene expression omnibus profile database revealed higher levels of RGS10 and RGS1 transcripts in peripheral blood mononuclear cells (PBMCs) in MS patients, suggesting potential functional roles for RGS proteins in MS etiology and/or progression.
  
  
  METHODS
  To define potential roles for RGS10 in regulating autoimmune responses, we evaluated RGS10-null and wild-type (WT) mice for susceptibility to experimental autoimmune encephalomyelitis (EAE), a widely studied model of MS. Leukocyte distribution and functional responses were assessed using biochemical, immunohistological, and flow cytometry approaches.
  
  
  RESULTS
  RGS10-null mice displayed significantly milder clinical symptoms of EAE with reduced disease incidence and severity, as well as delayed onset. We observed fewer CD3+ T lymphocytes and CD11b+ myeloid cells in the central nervous system (CNS) tissues of RGS10-null mice with myelin oligodendrocyte protein (MOG)35-55-induced EAE. Lymph node cells and splenocytes of immunized RGS10-null mice demonstrated decreased proliferative and cytokine responses in response to in vitro MOG memory recall challenge. In adoptive recipients, transferred myelin-reactive RGS10-null Th1 cells (but not Th17 cells) induced EAE that was less severe than their WT counterparts.
  
  
  CONCLUSIONS
  These data demonstrate a critical role for RGS10 in mediating autoimmune disease through regulation of T lymphocyte function. This is the first study ever conducted to elucidate the function of RGS10 in effector lymphocytes in the context of EAE. The identification of RGS10 as an important regulator of inflammation might open possibilities for the development of more specific therapies for MS.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Dr, Athens, GA, 30602, USA. jamlee@uga.edu.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: George T
authors.initials: GT
authors.lastname: Kannarkat
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Dr, Athens, GA, 30602, USA.
authors.forename: Jaegwon
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Joon Lee
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Kareem L
authors.initials: KL
authors.lastname: Graham
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Malú G
authors.initials: MG
authors.lastname: Tansey
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005620:Freund's Adjuvant / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D007116:Immunization, Passive; D007963:Leukocytes, Mononuclear / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D020710:RGS Proteins / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D020710:RGS Proteins; C491068:Rgs10 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant
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