Identity crisis of Th17 cells: many forms, many functions, many questions
Abstract
Th17 cells are a subset of CD4(+) effector T cells characterized by expression of the IL-17-family cytokines, IL-17A and IL-17F. Since their discovery nearly a decade ago, Th17 cells have been implicated in the regulation of dozens of immune-mediated inflammatory diseases and cancer. However, attempts to clarify the development and function of Th17 cells in human health and disease have generated as many questions as answers. On one hand, cytokine expression in Th17 cells appears to be remarkably dynamic and is subject to extensive regulation (both positive and negative) in tissue microenvironments. On the other hand, accumulating evidence suggests that the human Th17 subset is a heterogeneous population composed of several distinct pro- and anti-inflammatory subsets. Clearly, Th17 cells as originally conceived no longer neatly fit the long-standing paradigm of stable and irrepressible effector T cell function. Here we review current concepts surrounding human Th17 cells, with an emphasis on their plasticity, heterogeneity, and their many, tissue-specific functions. In spite of the challenges ahead, a comprehensive understanding of Th17 cells and their relationship to human disease is key to ongoing efforts to develop safer and more selective anti-inflammatory medicines.
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TH17 cells have been proposed to exist in 3 lineages: CCR6-dependent effector cells, memory cells, or IL-23R- and CXCR5-dependent follicular TH17 cells.
“TH17 cells have been proposed to exist in 3 lineages: CCR6-dependent effector cells, memory cells, or IL-23R- and CXCR5-dependent follicular TH17 cells (Awasthi and Kuchroo, 2009; Sundrud and Trivigno, 2013).”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Sundrud and Trivigno, 2013
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Giles, D. A., Moreno-Fernandez, M. E., Stankiewicz, T. E., Cappelletti, M., Huppert, S. S., Iwakura, Y., Dong, C., Shanmukhappa, S. K., & Divanovic, S. (2016) · PLOS ONE · doi:10.1371/journal.pone.0149783 · Cited by 116 · see citing works
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- Authors
- Sundrud, M. S., & Trivigno, C.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Sundrud, Mark S.
- ORCID
- Sundrud, Mark S.
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 25
- Issue
- 4
- Pages
- 263-272
- ISSN
- 1044-5323 (ISSN-L)
- OpenAlex
- W1983661116
- Cited by
- 77
- References
- 16
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 9
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- The Scripps Research Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- Th17 cells, IL-17A, IL-17F, T cell plasticity, T cell heterogeneity, cytokine expression regulation, tissue microenvironment, immune-mediated inflammatory diseases, tumor immunology, anti-inflammatory drug development, CD4+ effector T cells
- MeSH terms
- Animals, Humans, Phenotype, T-Lymphocyte Subsets, Th17 Cells
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