Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice

Charles O. Elson, Yingzi Cong, Casey T. Weaver, Trenton R. Schoeb, Terrill K. McClanahan, Robert B. Fick, Robert A. Kastelein

Research output: Contribution to journalArticlepeer-review

367 Scopus citations


Background & Aims: Interleukin (IL)-23 supports a distinct lineage of T cells producing IL-17 (Th17) that can mediate chronic inflammation. This study was performed to define the role of IL-23 and Th17 cells in chronic colitis in mice. Methods: Colitis was induced by transfer of a cecal bacterial antigen-specific C3H/HeJBir (C3Bir) CD4+ T-cell line to C3H/HeSnJ SCID mice. Cytokines were measured by flow cytometry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Monoclonal anti-IL-23p19 was administered at the same time as or 4 weeks after pathogenic CD4 T-cell transfer. A histopathology colitis score was assessed in a blinded fashion. Results: The pathogenic C3Bir CD4+ T-cell line contained more cells producing IL-17 than those producing interferon-γ and these were distinct subsets; after adoptive transfer to SCID recipients, Th17 cells were predominant in the lamina propria of mice with colitis. Bacteria-reactive CD4+ Th1 and Th17 lines were generated. The Th17 cells induced marked inflammation in a dose-dependent manner. Even at a dose as low as 104 cells/mouse, Th17 cells induced more severe disease than Th1 cells did at 106 cells/mouse. Monoclonal anti-IL-23p19 prevented and treated active colitis, with down-regulation of a broad array of inflammatory cytokines and chemokines in the colon. Anti-IL-23p19 induced apoptosis in colitogenic Th17 cells in vitro and in vivo. Conclusions: Bacterial-reactive CD4+ Th17 cells are potent effector cells in chronic colitis. Inhibition of IL-23p19 was effective in both prevention and treatment of active colitis. IL-23 is an attractive therapeutic target for inflammatory bowel disease.

Original languageEnglish (US)
Pages (from-to)2359-2370
Number of pages12
Issue number7
StatePublished - Jun 2007
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


Dive into the research topics of 'Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice'. Together they form a unique fingerprint.

Cite this