Syndecan 4 regulation of the development of autoimmune arthritis in mice by modulating B cell migration and germinal center formation

Tsutomu Endo, Koyu Ito, Junko Morimoto, Masashi Kanayama, Daichi Ota, Masahiro Ikesue, Shigeyuki Kon, Daisuke Takahashi, Tomohiro Onodera, Norimasa Iwasaki, Toshimitsu Uede

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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. Conclusion 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.

Original languageEnglish
Pages (from-to)2512-2522
Number of pages11
JournalArthritis and Rheumatology
Volume67
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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