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Proinflammatory T helper type 17 cells are effective B-cell helpers
Open accessAbstract
T helper type 17 (TH17) cells are highly proinflammatory effector T cells that are characterized by the production of high amounts of IL-17A, IL-17F, IL-21, and IL-22. Furthermore, TH17 cells have been associated with a number of autoimmune diseases. However, it is not clear whether TH17 cells can also serve as effective helper cells. Here we show that TH17 cells can function as B-cell helpers in that they not only induce a strong proliferative response of B cells in vitro but also trigger antibody production with class switch recombination in vivo. Transfer of TH17 cells into WT or T-cell receptor α–deficient mice, which lack endogenous T cells, induces a pronounced antibody response with preferential isotype class switching to IgG1, IgG2a, IgG2b, and IgG3, as well as the formation of germinal centers. Conversely, blockade of IL-17 signaling results in a significant reduction in both number and size of germinal centers. Whereas IL-21 is known to help B cells, IL-17 on its own drives B cells to undergo preferential isotype class switching to IgG2a and IgG3 subtypes. These observations provide insights into the unappreciated role of TH17 cells and their signature cytokines in mediating B-cell differentiation and class switch recombination.
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“multiple additional transcription factors were shown to be required for the expression of IL-17, including STAT3, IRF4, and BATF”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [19]
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“So far, IL-17 has mainly been described as a potent proinflammatory cytokine that acts on fibroblasts, stromal, epithelial, and endothelial cells, and some monocytes to stimulate the secretion of other proinflammatory mediators, such as IL-1, IL-6, chemokine ligand CXCL8 (also known as IL-8), CXCL1, TNF-α, and granulo…”
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Metadata
- Authors
- Mitsdoerffer, M., Lee, Y., Jäger, A., Kim, H.-J., Korn, T., Kolls, J. K., Cantor, H., Bettelli, E., & Kuchroo, V. K.
- Affiliations
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Technical University of Munich (DE)
- Louisiana State University Health Sciences Center New Orleans (US)
- Benaroya Research Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-07-26
- Volume
- 107
- Issue
- 32
- Pages
- 14292-14297
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2922571
- OpenAlex
- W2012706589
- Cited by
- 534
- References
- 36
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 40 · 2023: 27 · 2022: 23 · 2021: 46 · 2020: 40 · 2019: 28 · 2018: 23 · 2017: 31 · 2016: 50 · 2015: 34 · 2014: 29 · 2013: 42 · 2012: 37
- FWCI
- 16.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- National Institutes of Health (5r01hl061271-15, 7r01hl079142-05)
- National Heart, Lung, and Blood Institute (R01-HL061271, R01-HL079142)
- National Institute of Allergy and Infectious Diseases (P01AI045757, P01AI056299)
- National Institute of Neurological Disorders and Stroke (P01NS038037, R37NS030843, R01NS035685, R01NS059996)
- 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 › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- B cell help, class switch recombination, IL-17, IL-21, germinal center, antibody isotype switching, B cell proliferation, B cell differentiation
- MeSH terms
- Animals, Antibody Formation, B-Lymphocytes, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Immunoglobulin Isotypes, Inflammation, T-Lymphocytes, Immunoglobulin Class Switching, Interleukin-17, Cell Proliferation, Mice
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