Repositioning TH cell polarization from single cytokines to complex help
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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 are an independent T helper cell subset.
“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]
TGF-β and IL-6 are required to polarize naïve T cells into Th17 cells.
“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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Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity
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Current Progress in the Science of Novel Adjuvant Nano-Vaccine-Induced Protective Immune Responses
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Unique Features of the Immune Response in BTBR Mice
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The kinase ITK controls a Ca 2+ -mediated switch that balances T H 17 and T reg cell differentiation
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T Cell Extracellular Traps: Tipping the Balance Between Skin Health and Disease
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Perspectives on oral chronic graft-versus-host disease from immunobiology to morbid diagnoses
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Natural and Induced Tolerance to Hymenoptera Venom: A Single Mechanism?
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Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect
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Efficacy and Potential Mechanisms of Naringin in Atopic Dermatitis
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Adjuvant activity of tubeimosides by mediating the local immune microenvironment
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- 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
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