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Cited by 69T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisTGF-β signaling in diseases

TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells

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Mishra, Shruti, Liao, Wei, Liu, Yong, Yang, Ming, Ma, Chaoyu, Wu, Haijing, Zhao, Ming, Zhang, Xin +3 more·2021·Journal of Experimental Medicine
DOI 10.1084/jem.20200030PMC PMC7527976
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Abstract

In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3− CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.

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  • TGFB1 is critical for the differentiation of CD8+ Treg cells in mice.

    “Given that TGFB1 is critical for the differentiation of CD8+ Treg cells in mice73”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [73]

    The Results sections on TGF-β–controlled Helios expression and CD8+ Treg homeostasis show that TGF-β signaling helps maintain these cells in mice; added TGF-β1 also increased Helios expression in vitro. But the paper reports only a subtle population decrease with Tgfbr2 loss alone and a severe defect when both Tgfbr2 and Eomes are absent. It does not establish that TGFB1 itself is critical for CD8+ Treg differentiation. (LLM, conf=0.88)

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Authors
Mishra, S., Liao, W., Liu, Y., Yang, M., Ma, C., Wu, H., Zhao, M., Zhang, X., Qiu, Y., Lu, Q., & Zhang, N.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • Central South University (CN)
Corresponding author
Zhang, Nu
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2020-09-29
Volume
218
Issue
1
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20200030
PMC
PMC7527976
OpenAlex
W3091598844
Cited by
69
References
40
Citations by year
2026: 5 · 2025: 12 · 2024: 10 · 2023: 18 · 2022: 14 · 2021: 7 · 2020: 2
FWCI
3.59
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AI125701, AI139721, 1S10OD021805-01)
  • Cancer Research Institute
  • American Cancer Society (RSG-18-222-01-LIB)
  • National Natural Science Foundation of China (81522038, 81270024, 81220108017)
  • University of Texas Health Science Center at San Antonio
  • Mays Cancer Center (NIH-NCI P30 CA054174)
  • National Center for Advancing Translational Sciences (NIH-NCATS UL1 TR002645)
  • National Cancer Institute (P30 CA054174)
  • Cancer Prevention and Research Institute of Texas (RP160732)
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 › TGF-β signaling in diseases
Keywords
CD8+ regulatory T cells, CD4+ regulatory T cells, TGF-beta signaling, Eomesodermin, Foxp3, immune tolerance, autoimmunity, T cell differentiation
MeSH terms
Animals, Autoimmune Diseases, Mice, Transgenic, Signal Transduction, Transforming Growth Factor beta, CD8-Positive T-Lymphocytes, T-Box Domain Proteins, T-Lymphocytes, Regulatory, Mice

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