title: Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation.
abstract: OBJECTIVE
  Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines. Although syndecan 4 is known to be expressed on B cells, its role in immune responses remains unclear. The purpose of this study was to investigate the contribution of syndecan 4 to the development of immune arthritis in murine models.
  
  
  METHODS
  The clinical severity of 3 immunopathologically distinct models, collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and collagen antibody-induced arthritis (CAIA), was evaluated in wild-type (WT) mice and in syndecan 4-deficient (Sdc4(-/-) ) mice. Germinal center (GC) formation, B cell profiles, humoral immune responses, and B cell migration were analyzed during the course of CIA.
  
  
  RESULTS
  Sdc4(-/-) mice were resistant to the induction of CIA, which is T cell and B cell dependent, but AIA and CAIA, which are T cell dependent and T cell independent, respectively, occurred with equal frequency in WT mice and Sdc4(-/-) mice. Furthermore, Sdc4(-/-) mice had reduced numbers of B cells and deficient GC formation in draining lymph nodes (DLNs) during the course of CIA, resulting in reduced production of collagen-specific autoantibodies. Compared with B cells from WT mice, B cells from Sdc4(-/-) mice showed reduced chemotactic migration toward stromal cell-derived factor 1 (SDF-1) and reduced SDF-1-mediated Akt phosphorylation. Consistent with these findings, in vivo transfer experiments showed that fewer Sdc4(-/-) B cells than WT B cells were found in and around the follicles in the DLNs.
  
  
  CONCLUSIONS
  Our findings suggest that syndecan 4 contributes to the development of CIA by promoting GC formation and autoantibody production through its regulation of SDF-1-mediated B cell migration.
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Endo
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Koyu
authors.initials: K
authors.lastname: Ito
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Morimoto
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanayama
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Ota
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikesue
authors.affiliation: Hokkaido University, Graduate School of Pharmaceutical Sciences, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahashi
authors.affiliation: Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Institute for Genetic Medicine and Hokkaido University, Sapporo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054377:Chemokine CXCL12 / Q000276:immunology*; D024043:Collagen Type II / Q000633:toxicity; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053671:Syndecan-4 / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D054377:Chemokine CXCL12; D024043:Collagen Type II; C515256:Cxcl12 protein, mouse; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D051057:Proto-Oncogene Proteins c-akt