Induced CD4+Foxp3+Regulatory T Cells in Immune Tolerance
Abstract
Regulatory T lymphocytes are essential to maintain homeostasis of the immune system, limiting the magnitude of effector responses and allowing the establishment of immunological tolerance. Two main types of regulatory T cells have been identified—natural and induced (or adaptive)—and both play significant roles in tuning down effector immune responses. Adaptive CD4+Foxp3+regulatory T (iTreg) cells develop outside the thymus under a variety of conditions. These include not only antigen presentation under subimmunogenic or noninflammatory conditions, but also chronic inflammation and infections. We speculate that the different origin of iTreg cells (noninflammatory versus inflammatory) results in distinct properties, including their stability. iTreg cells are also generated during homeostasis of the gut and in cancer, although some cancers also favor expansion of natural regulatory T (nTreg) cells. Here we review how iTreg cells develop and how they participate in immunological tolerance, contrasting, when possible, iTreg cells with nTreg cells.
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Tregs exert immunosuppressive effects through multiple mechanisms, including cytokine secretion, metabolic disruption of effector T cells, and modulation of antigen-presenting cells.
“These cells exert immunosuppressive effects through multiple mechanisms, including cytokine secretion, metabolic disruption of effector T cells, and modulation of antigen-presenting cells (APCs) (Bilate and Lafaille 2012; Josefowicz et al. 2012; Wing et al. 2019).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Bilate and Lafaille 2012
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“These cells exert immunosuppressive effects through multiple mechanisms, including cytokine secretion, metabolic disruption of effector T cells, and modulation of antigen-presenting cells (APCs) (Bilate and Lafaille 2012; Josefowicz et al. 2012; Wing et al. 2019).”
- Authors
- Bilate, A. M., & Lafaille, J. J.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2012-04-23
- Volume
- 30
- Issue
- 1
- Pages
- 733-758
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2160458616
- Cited by
- 569
- References
- 11
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 23 · 2023: 26 · 2022: 32 · 2021: 33 · 2020: 35 · 2019: 41 · 2018: 37 · 2017: 43 · 2016: 49 · 2015: 55 · 2014: 64 · 2013: 67 · 2012: 24
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI041647, R01AI41647)
- 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 › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- induced regulatory T cells, natural regulatory T cells, Foxp3, immune tolerance, antigen presentation, chronic inflammation, infection, intestinal homeostasis, tumor immunology
- MeSH terms
- Animals, Antigen-Presenting Cells, Humans, Immune Tolerance, Lymphoid Tissue, CD4 Antigens, Adoptive Transfer, T-Lymphocytes, Regulatory, Forkhead Transcription Factors
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