A Critical Role of CD30 Ligand/CD30 in Controlling Inflammatory Bowel Diseases in Mice

Xun Sun, Shinichi Somada, Kensuke Shibata, Hiromi Muta, Hisakata Yamada, Hirofumi Yoshihara, Kuniomi Honda, Kazuhiko Nakamura, Ryhoichi Takayanagi, Kenzaburo Tani, Eckhard R. Podack, Yasunobu Yoshikai

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background & Aims: A CD30-ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice. Methods: Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS. Results: CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon γ were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice. Conclusions: These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.

Original languageEnglish (US)
Pages (from-to)447-458.e3
JournalGastroenterology
Volume134
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Sun, X., Somada, S., Shibata, K., Muta, H., Yamada, H., Yoshihara, H., Honda, K., Nakamura, K., Takayanagi, R., Tani, K., Podack, E. R., & Yoshikai, Y. (2008). A Critical Role of CD30 Ligand/CD30 in Controlling Inflammatory Bowel Diseases in Mice. Gastroenterology, 134(2), 447-458.e3. https://doi.org/10.1053/j.gastro.2007.11.004