Stability of the Regulatory T Cell Lineage in Vivo
Open accessAbstract
Self-Renewing T Cells: The homeostasis of cell populations within an organism can be achieved through a variety of mechanisms, including the differentiation of precursor populations, self-renewal of terminally differentiated cells, or by programming cells to be extremely long-lived. Regulatory T cells that express the transcription factor Foxp3 are critical for maintaining immune tolerance by preventing excessive inflammation and autoimmunity. Rubtsov et al. (p. 1667 ) now use genetic fate mapping and cell transfer studies in vivo to demonstrate that Foxp3-expressing cells are remarkably stable under both basal and inflammatory conditions. Thus, regulatory T cells appear to be maintained through self-renewal and should maintain their identity if used in adoptive cell therapies for treatment of autoimmunity or other inflammatory disorders.
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Tumor-infiltrating Tregs exhibit plasticity and have the ability to modify their features to function similarly to effector T cells while maintaining high amounts of FoxP3, known as Th-like Tregs.
“Tumor-infiltrating Tregs exhibit plasticity and have the ability to modify their features to function similarly to effector T cells while maintaining high amounts of FoxP3, known as Th-like Tregs [51].”
From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [51]
In the passage labeled Abstract (page unavailable), Tregs in mouse infection and Th1-inflammation experiments upregulated T-bet and CXCR3 while maintaining Foxp3. The paper does not study tumor-infiltrating Tregs or identify these cells as “Th-like Tregs”; it reports at best marginal increases in effector cytokines, not effector-T-cell-like function. (LLM, conf=0.85)
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Research works printed but not linked: 24
- [1]el Marjou F Genesis 39 186 7 2004 15282745
- [2]Dor Y Brown J Martinez OI Melton DA Nature 429 41 5 6 2004 15129273
- [3]Fontenot JD Gavin MA Rudensky AY Nature immunology 4 330 4 1 2003 12612578
- [4]Fontenot JD Immunity 22 329 3 1 2005 15780990
- [5]Hori S Takahashi T Sakaguchi S Adv Immunol 81 331 1 1 2003 14711059
- [6]Khattri R Cox T Yasayko SA Ramsdell F Nature immunology 4 337 4 1 2003 12612581
- [7]Kim JM Rasmussen JP Rudensky AY Nature immunology 8 191 2 1 2007 17136045
- [8]Apostolou I Sarukhan A Klein L von Boehmer H Nature immunology 3 756 8 1 2002 12089509
- [9]Hsieh CS Immunity 21 267 8 1 2004 15308106
- [10]Jordan MS Nature immunology 2 301 4 1 2001 11276200
- [11]Pacholczyk R Ignatowicz H Kraj P Ignatowicz L Immunity 25 249 8 1 2006 16879995
- [12]Williams LM Rudensky AY Nature immunology 8 277 3 1 2007 17220892
- [13]Liao W Nat Immunol 9 1288 11 2008 18820682 PMC2762127
- [14]Burchill MA Yang J Vogtenhuber C Blazar BR Farrar MA J Immunol 178 280 1 1 2007 17182565
- [15]Setoguchi R Hori S Takahashi T Sakaguchi S J Exp Med 201 723 3 7 2005 15753206 PMC2212841
- [16]Fontenot JD Rasmussen JP Gavin MA Rudensky AY Nat Immunol 6 1142 11 2005 16227984
- [17]Bayer AL Yu A Malek TR J Immunol 178 4062 4 1 2007 17371960
- [18]Malek TR J Clin Immunol 28 635 11 2008 18726679
- [19]Oldenhove G Immunity 31 772 11 20 2009 19896394 PMC2814877
- [20]Zhou X Bailey-Bucktrout S Jeker LT Bluestone JA Curr Opin Immunol 21 281 6 2009 19500966 PMC2733784
- [21]Koch MA Nat Immunol 10 595 6 2009 19412181 PMC2712126
- [22]Katz JD Wang B Haskins K Benoist C Mathis D Cell 74 1089 9 24 1993 8402882
- [25]Tsuji M Science 323 1488 3 13 2009 19286559
- [27]Zheng Y Nature 463 808 2 11 2010 20072126 PMC2884187
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- Authors
- Rubtsov, Y. P., Niec, R. E., Josefowicz, S., Li, L., Darce, J., Mathis, D., Benoist, C., & Rudensky, A. Y.
- Affiliations
- Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
- Memorial Sloan Kettering Cancer Center (US)
- Harvard University (US)
- Corresponding author
- Niec, Rachel E.
- Rudensky, Alexander Y.
- Venue
- Science
- Published
- 2010-09-24
- Volume
- 329
- Issue
- 5999
- Pages
- 1667-1671
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4262151
- OpenAlex
- W2034430001
- Cited by
- 730
- References
- 0
- Citations by year
- 2026: 27 · 2025: 35 · 2024: 41 · 2023: 30 · 2022: 29 · 2021: 43 · 2020: 44 · 2019: 41 · 2018: 39 · 2017: 40 · 2016: 43 · 2015: 56 · 2014: 57 · 2013: 69 · 2012: 64
- FWCI
- 27.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Institute of Allergy and Infectious Diseases (R01AI051530, R37AI034206, R37AI051530, AI51530)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- regulatory T cells, Treg cell stability, self-renewal, immune homeostasis, inflammation, autoimmunity, cell longevity
- MeSH terms
- Animals, Homeostasis, Inflammation, Leukocyte Count, Listeriosis, Listeria monocytogenes, Lymphoid Tissue, Mice, Transgenic, Tamoxifen, Autoimmunity, Cytokines, Cell Lineage, Cell Proliferation, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Gene Knock-In Techniques
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