Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis
Open accessAbstract
Significance: The Th17 subset of CD4 + T cells are important in the pathogenesis of inflammatory bowel disease (IBD), but the mechanisms of their actions, particularly the role of the development of IFN-γ–producing progeny of Th17 cells (Th1-like cells), are incompletely understood. Here, we show in a mouse model of Th17-driven IBD that transition of Th17 precursors to Th1-like cells is absolutely required for disease, because Th17 cells deficient in IFN-γ fail to induce intestinal inflammation. This transition is dependent on the transcription factors T-bet and, to a lesser extent, Stat4. These findings are relevant for clinical strategies that target IBD and suggest that focusing on both the Th17 and Th1-like arms of disease may be beneficial in therapy design.
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Th1-like cells derive from Th17 precursors contingent on intact IL-23-induced STAT4 activation and T-bet expression.
“Th1-like cells, which derive from Th17 precursors contingent on intact IL-23-induced STAT4 activation and T-bet 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 [73]
The Significance section (page unavailable) reports that Th1-like cells arise from Th17 precursors, that T-bet is critical, and that IL-23-driven STAT4 signaling is a major contributor. But it describes the transition as only partially dependent on STAT4: IFN-γ-producing cells remained when STAT4 was absent. Requiring intact STAT4 activation overstates that finding. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTh1-like cells were critical for colitis development.
“were critical for colitis development (73).”
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 [73]
Th17 cells assisted the development and/or survival of pathogenic Th1 cells that were unable to drive disease on their own.
“our previous studies showed that Th17 cells assisted the development and/or survival of pathogenic Th1 cells that were unable to drive disease on their own (73).”
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 [73]
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- Authors
- Harbour, S. N., Maynard, C. L., Zindl, C. L., Schoeb, T. R., & Weaver, C. T.
- Affiliations
- Department of Pathology
- University of Alabama at Birmingham (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-05-18
- Volume
- 112
- Issue
- 22
- Pages
- 7061-7066
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4460486
- OpenAlex
- W1516263086
- Cited by
- 427
- References
- 6
- Citations by year
- 2026: 29 · 2025: 32 · 2024: 40 · 2023: 54 · 2022: 54 · 2021: 46 · 2020: 38 · 2019: 30 · 2018: 40 · 2017: 30 · 2016: 29 · 2015: 5
- FWCI
- 17.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (DK071176, DK093015)
- Crohn's and Colitis Foundation of America (3381)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- Th17 cells, Th1 cells, colitis, inflammatory bowel disease, IL-17A, interferon-gamma, STAT4, T-bet, enteric microbiota, Th1 differentiation, pathogenesis
- MeSH terms
- T-bet Transcription Factor, Animals, Cell Differentiation, Interferon-gamma, Inflammatory Bowel Diseases, Mice, Knockout, Th1 Cells, Statistics, Nonparametric, Adoptive Transfer, T-Box Domain Proteins, STAT4 Transcription Factor, Mice, Th17 Cells
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