CD30 ligand is a new therapeutic target for central nervous system autoimmunity

Koji Shinoda, Xun Sun, Akiko Oyamada, Hisakata Yamada, Hiromi Muta, Eckhard R. Podack, Jun ichi Kira, Yasunobu Yoshikai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The CD30 ligand (CD30L)/CD30 axis plays a critical role in Th1 and Th17 cell differentiation. However, the role in the pathogenesis of central nervous system autoimmunity remains unknown. Here we show the resistance for experimental autoimmune encephalomyelitis (EAE) with markedly reduced induction of antigen-specific Th1 and Th17 cells in CD30L knockout mice. Bone marrow chimera experiments indicated that CD30L on bone marrow-derived cells were critical for the development of EAE and that CD30L reverse signaling in CD4 T cells was dispensable for the pathogenic Th17 cell differentiation at the induction phase. Adoptive transfer experiment revealed an additional role for CD30L in the environment at the effector phase. Invivo neutralization of CD30L by soluble murine CD30-Immunoglobulin fusion protein before disease onset or even after disease onset significantly ameliorated the clinical symptoms. These results indicate that CD30L/CD30 signaling is critically involved in antigen-specific CD4 T cell responses at both the induction and effector phase, thus could be a new target molecule for the treatment of central nervous system autoimmunity.

Original languageEnglish
Pages (from-to)14-23
Number of pages10
JournalJournal of Autoimmunity
Volume57
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

Fingerprint

CD30 Ligand
Autoimmunity
Central Nervous System
Th17 Cells
Th1 Cells
Autoimmune Experimental Encephalomyelitis
Therapeutics
Cell Differentiation
T-Lymphocytes
CD4 Antigens
Adoptive Transfer
Knockout Mice
Bone Marrow Cells
Immunoglobulins
Bone Marrow
Antigens

Keywords

  • CD30
  • CD30 ligand
  • CD30-Ig
  • EAE

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Shinoda, K., Sun, X., Oyamada, A., Yamada, H., Muta, H., Podack, E. R., ... Yoshikai, Y. (2015). CD30 ligand is a new therapeutic target for central nervous system autoimmunity. Journal of Autoimmunity, 57, 14-23. https://doi.org/10.1016/j.jaut.2014.11.005

CD30 ligand is a new therapeutic target for central nervous system autoimmunity. / Shinoda, Koji; Sun, Xun; Oyamada, Akiko; Yamada, Hisakata; Muta, Hiromi; Podack, Eckhard R.; Kira, Jun ichi; Yoshikai, Yasunobu.

In: Journal of Autoimmunity, Vol. 57, 01.02.2015, p. 14-23.

Research output: Contribution to journalArticle

Shinoda, K, Sun, X, Oyamada, A, Yamada, H, Muta, H, Podack, ER, Kira, JI & Yoshikai, Y 2015, 'CD30 ligand is a new therapeutic target for central nervous system autoimmunity', Journal of Autoimmunity, vol. 57, pp. 14-23. https://doi.org/10.1016/j.jaut.2014.11.005
Shinoda, Koji ; Sun, Xun ; Oyamada, Akiko ; Yamada, Hisakata ; Muta, Hiromi ; Podack, Eckhard R. ; Kira, Jun ichi ; Yoshikai, Yasunobu. / CD30 ligand is a new therapeutic target for central nervous system autoimmunity. In: Journal of Autoimmunity. 2015 ; Vol. 57. pp. 14-23.
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