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Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells
Open accessAbstract
Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome-wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3, and p300 at the Il23r, Il17a/f, and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program.
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“However, multiple studies have shown that IL-23 and RORγt, which are essential mediators of Th17 differentiation, are required for colitis [127, 131, 132].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [131]
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Metadata
- Authors
- Jain, R., Chen, Y., Kanno, Y., Joyce-Shaikh, B., Vahedi, G., Hirahara, K., Blumenschein, W. M., Sukumar, S., Haines, C. J., Sadekova, S., McClanahan, T. K., McGeachy, M. J., O’Shea, J. J., & Cua, D. J.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- National Institutes of Health (US)
- Corresponding author
- Cua, Daniel J.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 44
- Issue
- 1
- Pages
- 131-142
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC11608061
- OpenAlex
- W2196731768
- Cited by
- 167
- References
- 36
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 14 · 2023: 16 · 2022: 19 · 2021: 20 · 2020: 18 · 2019: 11 · 2018: 12 · 2017: 24 · 2016: 13
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIAAR041159)
- 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 › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-23, Blimp-1, Th17 cells, RORγt, STAT3, P300, transcriptional repression, autoimmune encephalomyelitis, cytokine gene expression, BCL6, Th17 cell differentiation
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Animals, Cell Differentiation, Cell Separation, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Regulation, Inflammation, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Transcription Factors, Transduction, Genetic, Mice, Knockout, Chromatin Immunoprecipitation, Mice, Interleukin-23, Th17 Cells, Real-Time Polymerase Chain Reaction
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