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 journalArticle

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Abstract

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
JournalGastroenterology
Volume132
Issue number7
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Interleukin-23
Th17 Cells
Colitis
T-Lymphocytes
Interleukins
Interleukin-17
Cytokines
Inflammation
Bacterial Antigens
Cell Line
Th1 Cells
SCID Mice
Adoptive Transfer
Inflammatory Bowel Diseases
Chemokines
Interferons
Real-Time Polymerase Chain Reaction
Flow Cytometry
Colon
Mucous Membrane

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Elson, C. O., Cong, Y., Weaver, C. T., Schoeb, T. R., McClanahan, T. K., Fick, R. B., & Kastelein, R. A. (2007). Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice. Gastroenterology, 132(7), 2359-2370. https://doi.org/10.1053/j.gastro.2007.03.104

Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice. / Elson, Charles O.; Cong, Yingzi; Weaver, Casey T.; Schoeb, Trenton R.; McClanahan, Terrill K.; Fick, Robert B.; Kastelein, Robert A.

In: Gastroenterology, Vol. 132, No. 7, 06.2007, p. 2359-2370.

Research output: Contribution to journalArticle

Elson, CO, Cong, Y, Weaver, CT, Schoeb, TR, McClanahan, TK, Fick, RB & Kastelein, RA 2007, 'Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice', Gastroenterology, vol. 132, no. 7, pp. 2359-2370. https://doi.org/10.1053/j.gastro.2007.03.104
Elson, Charles O. ; Cong, Yingzi ; Weaver, Casey T. ; Schoeb, Trenton R. ; McClanahan, Terrill K. ; Fick, Robert B. ; Kastelein, Robert A. / Monoclonal Anti-Interleukin 23 Reverses Active Colitis in a T Cell-Mediated Model in Mice. In: Gastroenterology. 2007 ; Vol. 132, No. 7. pp. 2359-2370.
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AU - McClanahan, Terrill K.

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