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Cited by 274Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation

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Chen, Zhi, Laurence, Arian, O'Shea, John J.·2007·Seminars in Immunology
DOI 10.1016/j.smim.2007.10.015PMC PMC2323678
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Abstract

The discovery of a new lineage of helper T cells that selectively produces interleukin (IL)-17 has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at how the complexity of selective regulation of cytokine gene expression might relate to lineage commitment, terminal differentiation and immunologic memory. Information continues to accumulate on factors that regulate Th17 differentiation at a rapid pace and a few lessons have emerged. Like other lineages, Th17 cells preferentially express a transcription factor, retinoic acid-related orphan receptor (ROR)gammat, whose expression seems to be necessary for IL-17 production. In addition, signals from the T-cell receptor are a critical aspect of controlling IL-17 production and the transcription factor nuclear factor of activated T cells (NFATs) appears to be another important regulator. IL-6, IL-21 and IL-23 are all cytokines that activate the transcription factor STAT3, which has been established to be necessary for multiple aspects of the biology of Th17 cells. Similarly, TGFbeta-1 is important for the differentiation of murine Th17 cells and inducible regulatory T cells (iTregs), but how it exerts its effect on IL-17 gene transcription is unknown and there are data indicating TGFbeta-1 is not required for human Th17 differentiation. The extent to which Th17 cells represent terminally differentiated cells or whether they retain plasticity and can develop into another lineage such as IFNgamma secreting Th1 cells is also unclear. Precisely how cytokines produced by this lineage are selectively expressed and selectively extinguished through epigenetic modifications is an area of great importance, but considerable uncertainty.

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  • STAT3 regulates both Th2 cell recruitment during allergic inflammation and the production of Th17 cells and the expansion and recruitment of neutrophils.

    “STAT3 is known to regulate both Th2 cell recruitment during allergic inflammation and the production of Th17 cells and the expansion and recruitment of neutrophils (Chen et al., 2007; Ma et al., 2008; Milner et al., 2008).”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Chen et al., 2007

    The Introduction identifies STAT3 as a critical regulator of Th17 differentiation. It also links enhanced STAT3 activity after SOCS3 deletion to inflammatory disease with neutrophil infiltration, but does not establish that STAT3 regulates neutrophil expansion or recruitment. Its discussion of Th2 cells does not address STAT3-dependent recruitment during allergic inflammation. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Chen, Z., Laurence, A., & O'Shea, J. J.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Seminars in Immunology
Publisher
Elsevier BV
Published
2007-12
Volume
19
Issue
6
Pages
400-408
ISSN
1044-5323 (ISSN-L)
DOI
10.1016/j.smim.2007.10.015
PMC
PMC2323678
OpenAlex
W1989694037
Cited by
274
References
7
Citations by year
2026: 5 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 11 · 2021: 12 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 20 · 2014: 13 · 2013: 24 · 2012: 21
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Seminars in Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (Z01AR041106)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
Th17 cells, Th17 cell differentiation, signal transduction, transcriptional regulation, RORγ, IL-17, NFAT, STAT3, interleukin-6, IL-21, IL-23, TGF-beta, inducible regulatory T cells, T cell receptor signaling, cytokine gene expression, epigenetic regulation, T cell plasticity, Th1 cells
MeSH terms
Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Humans, Receptors, Thyroid Hormone, Transcription, Genetic, Tretinoin, Signal Transduction, T-Lymphocyte Subsets, Cytokines, Transforming Growth Factor beta, Receptors, Retinoic Acid, Cell Lineage, Interleukin-17, Receptors, G-Protein-Coupled, Proto-Oncogene Protein c-ets-1, STAT3 Transcription Factor, Interferon Regulatory Factors, Nuclear Receptor Subfamily 1, Group F, Member 3

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