An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets
Open accessAbstract
Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear.Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells.We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, and Atf3) and 2 negative (Irf9 and Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10.We report two central regulators, Prdm1 and Maf, that cooperatively drive the expression of signature genes induced by IL-27 in type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3 + regulatory T cells.Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying ll10-deficient mice.Our work provides insights into IL-27-driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.
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Colonization of germ-free mice with SFB, but not other Clostridium or Bacteroides species, induces SFB-specific Th17 cells largely in the terminal ileum.
“Colonization of germ-free mice with SFB, but not other Clostridium or Bacteroides species, induced SFB-specific Th17 cells, largely in the terminal ileum, where SFB binds to the intestinal epithelium”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [72]
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References 138 · Cited by 91
Research works printed but not linked: 1
- Lewandoski M, Meyers EN, and Martin GR (1997). Analysis of Fgf8 gene function in vertebrate development. Cold Spring Harb. Symp. Quant. Biol 62, 159– 168. 9598348
- Authors
- Zhang, H., Madi, A., Yosef, N., Chihara, N., Awasthi, A., Pot, C., Lambden, C., Srivastava, A., Burkett, P. R., Nyman, J., Christian, E., Etminan, Y., Lee, A., Stroh, H., Xia, J., Karwacz, K., Thakore, P. I., Acharya, N., Schnell, A., Wang, C., Apetoh, L., Rozenblatt-Rosen, O., Anderson, A. C., Regev, A., & Kuchroo, V. K.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Madi, Asaf
- Regev, Aviv
- Kuchroo, Vijay K.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 33
- Issue
- 8
- Pages
- 108433
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7771052
- OpenAlex
- W3107426825
- Cited by
- 91
- References
- 138
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 12 · 2023: 23 · 2022: 24 · 2021: 6
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Update notices
- erratum (2025-03-25)
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- SERVAL (Université de Lausanne) (acceptedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc-nd)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- European Research Council (677251)
- Department of Science and Technology, Ministry of Science and Technology, India (CRG/2018/002653)
- National Institutes of Health (P01AI056299, P01AI039671, R01NS30843, P01AI073748, R01AI144166, P01AI129880, CA229400)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- IL-27, IL-10, transcriptional regulatory networks, T helper cell subsets, regulatory T cells, Foxp3+ regulatory T cells, Blimp-1, MAF, transcription factors, colitis, immune regulation, IRF9, IRF8
- MeSH terms
- Animals, Humans, Interleukin-10, Mice, Knockout, Th1 Cells, Mice, Gene Regulatory Networks, Interleukin-27
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