A dominant function for interleukin 27 in generating interleukin 10–producing anti-inflammatory T cells
Abstract
Regulatory T cells (T(reg) cells) expressing the transcription factor Foxp3 are key in maintaining the balance of immune homeostasis. However, distinct induced T regulatory type 1 (Tr1) cells that lack Foxp3 expression also regulate T cell function, mainly by producing the immunosuppressive cytokine interleukin 10 (IL-10). However, the factors required for the induction of IL-10-producing suppressive T cells are not fully understood. Here we demonstrate that dendritic cells modified by T(reg) cells induced the generation of IL-10-producing Tr1 cells. The differentiation of naive CD4+ T cells into IL-10-producing cells was mediated by IL-27 produced by the T(reg) cell-modified dendritic cells, and transforming growth factor-beta amplified the generation of induced IL-10+ Tr1 cells by IL-27. Thus, IL-27 and transforming growth factor-beta promote the generation of IL-10-producing Tr1 cells.
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Selective IL-23 inhibitors (tildrakizumab, risankizumab, guselkumab) targeting IL-23 p19 are more effective than TNF inhibitors and IL-23/IL-12 inhibitors.
“More recently, selective IL-23 inhibitors (tildrakizumab, risankizumab, and guselkumab) that specifically target the IL-23 p19 subunit were found to be more effective than TNF inhibitors [137] and IL-23/IL-12 inhibitors [28, 138].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [137]
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- Authors
- Awasthi, A., Carrier, Y., Peron, J. P. S., Bettelli, E., Kamanaka, M., Flavell, R. A., Kuchroo, V. K., Oukka, M., & Weiner, H. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Universidade de São Paulo (BR)
- Yale University (US)
- Corresponding author
- Oukka, Mohamed
- Weiner, Howard L
- ORCID
- Venue
- Nature Immunology
- Published
- 2007-11-11
- Volume
- 8
- Issue
- 12
- Pages
- 1380-1389
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2004660702
- Cited by
- 804
- References
- 50
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 29 · 2023: 31 · 2022: 19 · 2021: 36 · 2020: 39 · 2019: 24 · 2018: 36 · 2017: 54 · 2016: 59 · 2015: 53 · 2014: 47 · 2013: 68 · 2012: 58
- FWCI
- 20.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- U.S. Public Health Service (1R01A144880-03, 2P01A139671-07)
- National Institute of Allergy and Infectious Diseases (R01AI073542, AI043458, R01AI043458)
- National Institute of Neurological Disorders and Stroke (1P01 NS38037-04, 2R37NS30843-11, NS038037, R01NS046414, P01NS038037, R37NS030843, R01NS035685, R01NS059996, 2R01NS35685-06, R01NS045937)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-27, IL-10, induced regulatory T cells, Foxp3, dendritic cells, TGF-beta, CD4+ T cell differentiation, immune homeostasis
- MeSH terms
- Animals, Humans, Lymphocyte Activation, Transforming Growth Factor beta, Interleukin-10, Interleukin-17, T-Lymphocytes, Regulatory
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