CD30 ligand/CD30 interaction is involved in pathogenesis of inflammatory bowel disease

Shinichi Somada, Hiromi Muta, Kazuhiko Nakamura, Xun Sun, Kuniomi Honda, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi, Yasunobu Yoshikai, Eckhard R. Podack, Kenzaburo Tani

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background and Aims Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 ligand (CD30L)/CD30 signals in intestinal mucosal damage. Methods Serum sCD30 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and healthy individuals was assessed. A model of enteritis induced by anti-CD3 monoclonal antibody injection was studied in wild-type mice and in CD30L knockout mice. Results Increased sCD30 was observed in UC and CD patients, and the level was correlated with disease activity in both conditions. In a murine model of enteritis, histological intestinal damage was significantly reduced in CD30L knockout mice with decreased Th1 and Th17 cytokine levels. Moreover, blocking of CD30L/CD30 signals by CD30-immunoglobulin (CD30-Ig) resulted in reduced inflammation. Conclusions Increased sCD30 expression correlating with disease activity suggested that CD30L/CD30 signals play an important role in pathogenesis of UC and CD. CD30L/CD30 pathway acts as an accelerator of enteritis in a murine disease model. Successful blockade of enteritis by CD30-Ig suggests a potential tool for future therapy of inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)2031-2037
Number of pages7
JournalDigestive Diseases and Sciences
Volume57
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

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Keywords

  • CD30
  • CD30 ligand
  • Crohn's disease
  • Inflammatory bowel disease
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Somada, S., Muta, H., Nakamura, K., Sun, X., Honda, K., Ihara, E., Akiho, H., Takayanagi, R., Yoshikai, Y., Podack, E. R., & Tani, K. (2012). CD30 ligand/CD30 interaction is involved in pathogenesis of inflammatory bowel disease. Digestive Diseases and Sciences, 57(8), 2031-2037. https://doi.org/10.1007/s10620-012-2129-0