Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells
Open accessAbstract
FOXP3+ regulatory T (Treg) cells are a broadly acting and potent anti-inflammatory population of CD4+ T cells essential for maintaining immune homeostasis and preventing debilitating autoimmunity. Based on chemokine receptor expression, we identified distinct populations of Treg cells in human blood expected to colocalize with different Th cell subsets. Although each population was functionally suppressive, they displayed unique patterns of pro- and anti-inflammatory cytokine production, differentially expressed lineage-specifying transcription factors, and responded differently to antigens associated with Th1 and Th17 responses. These results highlight a previously unappreciated degree of phenotypic and functional diversity in human Treg cells that allows subsets with unique specificities and immunomodulatory functions to be targeted to defined immune environments during different types of inflammatory responses.
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Th1-like Tregs lose their inhibitory function and secrete the pro-inflammatory cytokine IFN-γ.
“They lose their inhibitory function and secrete the pro-inflammatory cytokine IFN-γ [54].”
From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [54]
The Results report that Th1-like Tregs produce IFN-γ, but also that all tested Treg subsets blocked T-cell proliferation. The Discussion states that each subset was suppressive in vitro and that IFN-γ-producing Tregs appear to retain regulatory activity, contrary to the claim that they lose inhibitory function. Page numbers were not available in our copy. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredTh1, Th2, Th17, and Th17.1-like Tregs can be detected in peripheral blood and identified on the basis of expression of Th-cell-associated chemokine receptors and/or transcription factors.
“Specifically, Th1, Th2, Th17, and Th17.1-like Tregs can be detected in peripheral blood and identified on the basis of expression of Th-cell-associated chemokine receptors and/or transcription factors [370].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [370]
The Introduction and Results identify Th1-, Th2-, and Th17-like Tregs in human peripheral blood using chemokine-receptor profiles; the Results also describe associated transcription factors. The paper names Th22-like, not Th17.1-like, Tregs as its fourth subset, so it does not support that part of the claim. Page numbers were not available in our copy. (LLM, conf=0.90)
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- Authors
- Duhen, T., Duhen, R., Lanzavecchia, A., Sallusto, F., & Campbell, D. J.
- Affiliations
- University of Washington (US)
- Institute for Research in Biomedicine (CH)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-05-10
- Volume
- 119
- Issue
- 19
- Pages
- 4430-4440
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3362361
- OpenAlex
- W1991748190
- Cited by
- 413
- References
- 51
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 31 · 2023: 20 · 2022: 33 · 2021: 31 · 2020: 33 · 2019: 35 · 2018: 31 · 2017: 33 · 2016: 27 · 2015: 30 · 2014: 33 · 2013: 24 · 2012: 22
- FWCI
- 15.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI067750, R56AI067750, R01AI067750)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK072295, R01DK072295)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055695, AR055695)
- 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 › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- Foxp3+ regulatory T cells, chemokine receptor expression, Th1 cells, Th17 cells, cytokine production, transcription factors, antigen responsiveness, immune homeostasis, autoimmunity, immunomodulation
- MeSH terms
- Anti-Inflammatory Agents, Cells, Cultured, T-Lymphocytes, Helper-Inducer, Humans, Phenotype, Transcription Factors, CD4-Positive T-Lymphocytes, Cytokines, Inflammation Mediators, T-Cell Antigen Receptor Specificity, T-Lymphocytes, Regulatory, Forkhead Transcription Factors
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