The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Doreau, A., Bélot, A., Bastid, J., Riche, B., Trescol-Biémont, M.-C., Ranchin, B., Fabien, N., Cochat, P., Pouteil‐Noble, C., Trolliet, P., et al. (2009) · Nature Immunology · doi:10.1038/ni.1741 · Cited by 448
RetractedKorn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Self-citationInterferon-γ and B Cell Stimulatory Factor-1 Reciprocally Regulate Ig Isotype Production
Snapper, C. M., & Paul, W. E. (1987) · Science · doi:10.1126/science.3107127 · Cited by 1,927
CD4 T cells: fates, functions, and faults
Zhu, J., & Paul, W. E. (2008) · Blood · doi:10.1182/blood-2008-05-078154 · Cited by 1,915
IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells
Korn, T., Bettelli, E., Gao, W., Awasthi, A., Jäger, A., Strom, T. B., Oukka, M., & Kuchroo, V. K. (2007) · Nature · doi:10.1038/nature05970 · Cited by 1,896
Self-citationJohnston, R. J., Poholek, A. C., DiToro, D., Yusuf, I., Eto, D., Barnett, B., Dent, A. L., Craft, J., & Crotty, S. (2009) · Science · doi:10.1126/science.1175870 · Cited by 1,626
Plasticity of CD4+ T Cell Lineage Differentiation
Zhou, L., Chong, M. M. W., & Littman, D. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.001 · Cited by 1,551
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2593 · Cited by 1,526 · cited 1×
“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…”
BackgroundBcl6 mediates the development of T follicular helper cells
Nurieva, R. I., Chung, Y., Martinez, G. J., Yang, X. O., Tanaka, S., Matskevitch, T. D., Wang, Y.-H., & Dong, C. (2009) · Science · doi:10.1126/science.1176676 · Cited by 1,506
Structure and signalling in the IL-17 receptor family
Gaffen, S. L. (2009) · Nature reviews. Immunology · doi:10.1038/nri2586 · Cited by 1,475
The Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment
Yu, D., Rao, S., Tsai, L. M., Lee, S. K., He, Y., Sutcliffe, E. L., Srivastava, M., Linterman, M. A., Zheng, L., Simpson, N., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.07.002 · Cited by 1,260
Nurieva, R. I., Chung, Y., Hwang, D., Yang, X. O., Kang, H. S., Ma, L., Wang, Y.-H., Watowich, S. S., Jetten, A. M., Tian, Q., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.009 · Cited by 1,205
Wei, G., Wei, L., Zhu, J., Zang, C., Hu-Li, J., Yao, Z., Cui, K., Kanno, Y., Roh, T.-Y., Watford, W. T., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.12.009 · Cited by 1,152
Late Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053
Self-citationHerpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor
Yao, Z., Fanslow, W. C., Seldin, M. F., Rousseau, A.-M., Painter, S. L., Comeau, M. R., Cohen, J. I., & Spriggs, M. K. (1995) · Immunity · doi:10.1016/1074-7613(95)90070-5 · Cited by 1,011
Ishigame, H., Kakuta, S., Nagai, T., Kadoki, M., Nambu, A., Komiyama, Y., Fujikado, N., Tanahashi, Y., Akitsu, A., Kotaki, H., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.009 · Cited by 1,004 · cited 2×
“Only a limited number of IL-17– induced genes have been documented in lymphocytes, and these genes are distinct from those induced by IL-17 in other cell types (12, 17).”
BackgroundA Critical Role for IL-21 in Regulating Immunoglobulin Production
Ozaki, K., Spolski, R., Feng, C. G., Qi, C.-F., Cheng, J., Sher, A., Morse, H. C., Liu, C., Schwartzberg, P. L., & Leonard, W. J. (2002) · Science · doi:10.1126/science.1077002 · Cited by 978
IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses
Linterman, M. A., Beaton, L., Yu, D., Ramiscal, R. R., Srivastava, M., Hogan, J. J., Verma, N. K., Smyth, M. J., Rigby, R. J., & Vinuesa, C. G. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091738 · Cited by 839
Bettelli, E., Pagany, M., Weiner, H. L., Linington, C., Sobel, R. A., & Kuchroo, V. K. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021603 · Cited by 828
Self-citationZotos, D., Coquet, J. M., Zhang, Y., Light, A., D’Costa, K., Kallies, A., Corcoran, L. M., Godfrey, D. I., Toellner, K., Smyth, M. J., et al. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091777 · Cited by 815
Cytokine-secreting follicular T cells shape the antibody repertoire
Reinhardt, R. L., Liang, H.-E., & Locksley, R. M. (2009) · Nature Immunology · doi:10.1038/ni.1715 · Cited by 807
A Fundamental Role for Interleukin-21 in the Generation of T Follicular Helper Cells
Vogelzang, A., McGuire, H. M., Yu, D., Sprent, J., Mackay, C. R., & King, C. (2008) · Immunity · doi:10.1016/j.immuni.2008.06.001 · Cited by 762
Hsu, H., Yang, P., Wang, J., Wu, Q., Myers, R. C., Chen, J., Yi, J. S., Guentert, T., Tousson, A., Stanus, A. L., et al. (2007) · Nature Immunology · doi:10.1038/ni1552 · Cited by 732
Self-citationBauquet, A. T., Jin, H., Paterson, A. M., Mitsdoerffer, M., Ho, I.-C., Sharpe, A. H., & Kuchroo, V. K. (2009) · Nature Immunology · doi:10.1038/ni.1690 · Cited by 713
Self-citationOzaki, K., Spolski, R., Ettinger, R., Kim, H.-P., Wang, G., Qi, C.-F., Hwu, P., Shaffer, D. J., Akilesh, S., Roopenian, D. C., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.9.5361 · Cited by 668
Self-citationT Follicular Helper (TFH) Cells in Normal and Dysregulated Immune Responses
King, C., Tangye, S. G., & Mackay, C. R. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090344 · Cited by 653
Odegard, J., Marks, B. R., DiPlacido, L. D., Poholek, A. C., Kono, D. H., Dong, C., Flavell, R. A., & Craft, J. E. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080840 · Cited by 420
Kuchen, S., Robbins, R., Sims, G. P., Sheng, C., Phillips, T. M., Lipsky, P. E., & Ettinger, R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.9.5886 · Cited by 340
Jin, H., Carrió, R., Yu, A., & Malek, T. R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.1.657 · Cited by 259
Toellner, K., Luther, S. A., Sze, D., Choy, K. W., Taylor, D. R., MacLennan, I. C. M., & Acha‐Orbea, H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.8.1193 · Cited by 234
Adelmann, M., Wood, J., Benzel, I. M., Fiori, P., Lassmann, H., Matthieu, J., Gardinier, M. V., Dornmair, K., & Linington, C. (1995) · Journal of Neuroimmunology · doi:10.1016/0165-5728(95)00124-7 · Cited by 232
The role of IL‐21 in regulating B‐cell function in health and disease
Ettinger, R., Kuchen, S., & Lipsky, P. E. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00631.x · Cited by 216
IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells
Mehta, D. S., Wurster, A. L., Whitters, M. J., Young, D. A., Collins, M. A., & Grusby, M. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.4111 · Cited by 198
Smith, K. M., Pottage, L., Thomas, E. R., Leishman, A. J., Doig, T. N., Xu, D., Liew, F. Y., & Garside, P. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.6.3136 · Cited by 185
Distinctive characteristics of germinal center B cells
Han, S., Zheng, B. Q., Takahashi, Y., & Kelsoe, G. H. (1997) · Seminars in Immunology · doi:10.1006/smim.1997.0081 · Cited by 90
In Vivo Generated Th1 Cells Can Migrate to B Cell Follicles to Support B Cell Responses
Smith, K. M., Brewer, J. M., Rush, C. M., Riley, J., & Garside, P. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1640 · Cited by 52
Cited by
Sorted by citations
Follicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289
Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response
Hajishengallis, G. (2014) · Trends in Immunology · doi:10.1016/j.it.2013.09.001 · Cited by 1,150
Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions
Chung, Y., Tanaka, S., Chu, F., Nurieva, R. I., Martinez, G. J., Rawal, S., Wang, Y.-H., Lim, H., Reynolds, J. M., Zhou, X.-H., et al. (2011) · Nature Medicine · doi:10.1038/nm.2426 · Cited by 1,120
Programming the magnitude and persistence of antibody responses with innate immunity
Kasturi, S. P., Skountzou, I., Albrecht, R. A., Koutsonanos, D., Tang, H., Nakaya, H. I., Ravindran, R., Stewart, S. M., Alam, M. S., Kwissa, M., et al. (2011) · Nature · doi:10.1038/nature09737 · Cited by 995
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
