Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells
Open accessAbstract
Mutations in the IL23R gene are linked to inflammatory bowel disease susceptibility. Experimental models have shown that interleukin-23 (IL-23) orchestrates innate and T cell-dependent colitis; however, the cell populations it acts on to induce intestinal immune pathology are unknown. Here, using Il23r(-/-) T cells, we demonstrated that T cell reactivity to IL-23 was critical for development of intestinal pathology, but not for systemic inflammation. Through direct signaling into T cells, IL-23 drove intestinal T cell proliferation, promoted intestinal Th17 cell accumulation, and enhanced the emergence of an IL-17A(+)IFN-gamma(+) population of T cells. Furthermore, IL-23R signaling in intestinal T cells suppressed the differentiation of Foxp3(+) cells and T cell IL-10 production. Although Il23r(-/-) T cells displayed unimpaired Th1 cell differentiation, these cells showed impaired proliferation and failed to accumulate in the intestine. Together, these results highlight the multiple functions of IL-23 signaling in T cells that contribute to its colitogenic activity.
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Subsequent studies established an essential role for the IL-23-Th17 axis in disease pathogenesis.
“whereas subsequent studies established an essential role for the IL-23–Th17 axis in disease pathogenesis (15, 72).”
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 [15]
The Results section ('IL-23R Expression on T Cells Is Required for Intestinal but Not Systemic Inflammation'; page unavailable) finds that T-cell IL-23R signaling is required for intestinal inflammation and is associated with reduced Th17-related responses when absent. The Discussion says IL-23-dependent Th17-like cells are suggested to play an important role in pathogenesis; it does not establish that the entire IL-23–Th17 axis is essential to disease pathogenesis generally. (LLM, conf=0.86)
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- Authors
- Ahern, P. P., Schiering, C., Buonocore, S., McGeachy, M. J., Cua, D. J., Maloy, K. J., & Powrie, F.
- Affiliations
- University of Oxford (GB)
- John Radcliffe Hospital (GB)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Powrie, Fiona
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 33
- Issue
- 2
- Pages
- 279-288
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3078329
- OpenAlex
- W2068133245
- Cited by
- 528
- References
- 9
- Citations by year
- 2026: 14 · 2025: 30 · 2024: 22 · 2023: 30 · 2022: 21 · 2021: 23 · 2020: 18 · 2019: 36 · 2018: 30 · 2017: 30 · 2016: 37 · 2015: 47 · 2014: 45 · 2013: 48 · 2012: 42
- FWCI
- 19.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Immunity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Wellcome Trust (086354)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-23, IL23R, intestinal inflammation, inflammatory bowel disease, Th17 cells, IL-17A, Foxp3+ regulatory T cells, IL-10, Th1 cells, T cell proliferation, colitis, T cell signaling
- MeSH terms
- Animals, Cells, Cultured, Colitis, Mice, Inbred C57BL, T-Lymphocytes, Receptors, Interleukin, Mice, Knockout, Cell Proliferation, Mice, Interleukin-23
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