Cited by 509T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisDevelopmental Biology and Gene Regulation

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Helper T cell differentiation

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

DOI 10.1038/s41423-019-0220-6PMC PMC6804569

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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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Authors: Saravia, J., Chapman, N. M., & Chi, H.
Affiliations: St. Jude Children's Research Hospital (US)
Corresponding author: Chi, Hongbo
ORCID: Saravia, Jordy
Chapman, Nicole M.
Chi, Hongbo
Venue: Cellular & Molecular Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-03-12
Volume: 16
Issue: 7
Pages: 634-643
ISSN: 1672-7681 (ISSN-L)
2042-0226
DOI: 10.1038/s41423-019-0220-6
PMC: PMC6804569
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
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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