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Repositioning TH cell polarization from single cytokines to complex help
Open accessAbstract
When helper T (T H) cell polarization was initially described three decades ago, the T H cell universe grew dramatically. New subsets were described based on their expression of few specific cytokines. Beyond T H 1 and T H 2 cells, this led to the coining of various T H 17 and regulatory (T reg) cell subsets as well as T H 22, T H 25, follicular helper (T FH), T H 3, T H 5 and T H 9 cells. High-dimensional single-cell analysis revealed that a categorization of T H cells into a single-cytokine-based nomenclature fails to capture the complexity and diversity of T H cells. Similar to the simple nomenclature used to describe innate lymphoid cells (ILCs), we propose that T H cell polarization should be categorized in terms of the help they provide to phagocytes (type 1), to B cells, eosinophils and mast cells (type 2) and to non-immune tissue cells, including the stroma and epithelium (type 3). Studying T H cells based on their helper function and the cells they help, rather than phenotypic features such as individual analyzed cytokines or transcription factors, better captures T H cell plasticity and conversion as well as the breadth of immune responses in vivo.
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“Th17 cells were established as an independent T helper cell subset with the discovery of signature cytokines IL-17A, IL-17F, and IL-22, lineage-specific differentiation factors, and dedicated or “master” transcription factors”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [14]
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“In 2006, the cytokines TGF-β and IL-6 were described as differentiation factors required to polarize naïve T cells into Th17 cells”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [14]
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Metadata
- Authors
- Tuzlak, S., Dejean, A. S., Iannacone, M., Quintana, F. J., Waisman, A., Ginhoux, F., Korn, T., & Becher, B.
- Affiliations
- University of Zurich (CH)
- Centre National de la Recherche Scientifique (FR)
- Vita-Salute San Raffaele University (IT)
- Broad Institute (US)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Agency for Science, Technology and Research (SG)
- TUM Klinikum (DE)
- Corresponding author
- Korn, Thomas
- Becher, Burkhard
- ORCID
- Venue
- Nature Immunology
- Published
- 2021-09-20
- Volume
- 22
- Issue
- 10
- Pages
- 1210-1217
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W3200319266
- Cited by
- 171
- References
- 148
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 44 · 2023: 39 · 2022: 43 · 2021: 5
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- HAL (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- National Multiple Sclerosis Society (RG4111A1, PA-1604-08459)
- European Molecular Biology Organization (RG4111A1)
- Gilead Sciences
- Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
- International Progressive MS Alliance (PA-1604-08459)
- Multiple Sclerosis Society (PA-1604-08459)
- Deutsche Forschungsgemeinschaft (SFB 1054, CRC1292, TRR‐156, EXC 2145, TRR-274, 390857198, TRR128, TRR156, CRC1292)
- Agence Nationale de la Recherche (ANR-16-CE15-0007)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (170320, 188450, 183478)
- Ministero della Salute (2018-, COVID-2020-12371617, RF-2018, RF-2018-12365801)
- Associazione Italiana per la Ricerca sul Cancro (19891 and 22737, 22737, 19891)
- National Institutes of Health (733 310030_170320, ES02530, RG4111A1, H2020, ES029136)
- Horizon 2020 Framework Programme (847782, 882424, 826121)
- Biomedical Research Council
- National Institute of Allergy and Infectious Diseases (R01AI126880)
- National Institute of Neurological Disorders and Stroke (R01NS102807)
- H2020 European Research Council (725038, 957502, 647215)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- T helper cell polarization, T helper subsets, helper functions, T helper type 1 cells, Th2 cells, T cell diversity, single-cell analysis, T cell help to B cells
- MeSH terms
- Cell Plasticity, Animals, B-Lymphocytes, Eosinophils, Epithelium, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Innate, Lymphocytes, Phagocytes, Cytokines
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 ›
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