Monoclonal Anti–Interleukin 23 Reverses Active Colitis in a T Cell–Mediated Model in Mice
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-gamma 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 10(4) cells/mouse, Th17 cells induced more severe disease than Th1 cells did at 10(6) 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 effect…
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Ongoing IL-6 signaling is indispensable and foundational, acting upstream of IL-23 via its unique function to sustain RORγt expression and thereby IL-23R expression.
“Although it has been reported that IL-23 signaling is important for the maintenance of Th17 cells (18, 19, 21), we find that ongoing IL-6 signaling is indispensable and foundational, acting upstream of IL-23 via its unique function to sustain RORγt expression and thereby IL-23R expression.”
From T <sub>H</sub> 17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity (2020) · cites this paper as [18]
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- Authors
- Elson, C. O., Cong, Y., Weaver, C. T., Schoeb, T. R., McClanahan, T. K., Fick, R. B., & Kastelein, R. A.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Elson, Charles O.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 132
- Issue
- 7
- Pages
- 2359-2370
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1964300433
- Cited by
- 453
- References
- 6
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 10 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 24 · 2015: 26 · 2014: 23 · 2013: 35 · 2012: 46
- FWCI
- 27.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK064400, P01DK071176, DK064400, P01DK044240)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-23, IL-23p19, Th17 cells, IL-17, chronic colitis, inflammatory bowel disease, anti-IL-23 monoclonal antibody, adoptive T cell therapy, CD4+ T cells, lamina propria inflammation, Th1 cells, apoptosis, chemokines, inflammatory cytokines
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Bacterial, Cecum, Cell Line, Colitis, Dendritic Cells, Disease Models, Animal, Interferon-gamma, Mice, Inbred C3H, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Mice, SCID, Interleukin-12, Adoptive Transfer, Interleukin-17, Mice, Interleukin-23, Interleukin-23 Subunit p19
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