title: Differential expression of SOCS1 in macrophages in relapsing-remitting and chronic EAE and its role in disease severity.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated neuroinflammatory disease that is often used as a model of multiple sclerosis. EAE can follow either relapsing-remitting (RR) or chronic (CH) courses, yet the factors responsible for differentially inducing these forms of disease remain largely unknown. Proinflammatory cytokines play an important role in EAE, and signaling by these cytokines can be negatively regulated by the suppressor of cytokine signaling 1 protein (SOCS1). We assessed if differential expression of SOCS1 could contribute to the clinical course of RR and CH forms of EAE induced in the same mouse strain (C57BL/6) using the same myelin antigen (myelin oligodendrocyte glycoprotein). We show that SOCS1 mRNA levels are significantly elevated in the spinal cord in early stages of both RR- and CH-EAE. SOCS1 protein is highly expressed in immune cells in EAE lesions in the spinal cord, with expression predominantly localized within macrophages. Importantly, the number of Mac-1(+) macrophages expressing SOCS1 at the peak stage of RR disease is three-fold greater than in CH-EAE. Furthermore, the macrophage effector molecule iNOS, whose expression is regulated by SOCS1, is significantly reduced at the peak of RR- versus CH-EAE. Finally, the administration of a SOCS1-mimetic peptide reduces disease severity in the CH-EAE model. Thus, the differential expression of SOCS1 may contribute to the development of RR and CH forms of EAE.
authors.affiliation: Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Berard
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Kerr
authors.forename: Howard M
authors.initials: HM
authors.lastname: Johnson
authors.forename: Samuel
authors.initials: S
authors.lastname: David
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D037502:Galectin 3 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016827:CD8 Antigens; D037502:Galectin 3; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant; D052247:Nitric Oxide Synthase Type II