Cited by 489T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisDevelopmental Biology and Gene Regulation

Helper T cell differentiation

Open access
Saravia, Jordy, Chapman, Nicole M., Chi, Hongbo·2019·Cellular & Molecular Immunology

Abstract

CD4+ T helper cells are key regulators of host health and disease. In the original model, specialized subsets of T helper cells are generated following activation through lineage-specifying cytokines and transcriptional programs, but recent studies have revealed increasing complexities for CD4+ T-cell differentiation. Here, we first discuss CD4+ T-cell differentiation from a historical perspective by highlighting the major studies that defined the distinct subsets of T helper cells. We next describe the mechanisms underlying CD4+ T-cell differentiation, including cytokine-induced signaling and transcriptional networks. We then review current and emerging topics of differentiation, including the plasticity and heterogeneity of T cells, the tissue-specific effects, and the influence of cellular metabolism on cell fate decisions. Importantly, recent advances in cutting-edge approaches, especially systems biology tools, have contributed to new concepts and mechanisms underlying T-cell differentiation and will likely continue to advance this important research area of adaptive immunity.

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Crossref · 10.1038/s41423-019-0220-6

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  • The current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities.

    “However, the current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities [177, 178].”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [178]

    The Introduction (page not provided) describes plasticity: differentiated CD4+ T cells can adopt alternative expression profiles and produce cytokines associated with other subsets. It also describes a continuum of developmental states and a spectrum of functional states in TH17 cells. It does not establish the broader assertion that CD4+ T helper subsets are not separate lineages at all. (LLM, conf=0.86)

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Authors
Saravia, J., Chapman, N. M., & Chi, H.
Affiliations
St. Jude Children's Research Hospital (US)
Corresponding author
Chi, Hongbo
Venue
Cellular & Molecular Immunology
Published
2019-03-12
Volume
16
Issue
7
Pages
634-643
ISSN
  • 1672-7681 (ISSN-L)
  • 2042-0226
OpenAlex
W2921191661
Cited by
489
References
218
Citations by year
2026: 33 · 2025: 85 · 2024: 114 · 2023: 94 · 2022: 80 · 2021: 44 · 2020: 34 · 2019: 5
FWCI
3.51
Type
journal article
Language
en
Open access
Locations
  • Cellular and Molecular Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Foundation for the National Institutes of Health
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
CD4+ T helper cells, T helper cell differentiation, T helper cell subsets, transcriptional regulatory networks, T cell plasticity, T cell heterogeneity, cellular metabolism, cell fate determination, systems biology
MeSH terms
Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Humans, Cytokines, Cell Lineage, Gene Regulatory Networks, Adaptive Immunity

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