The dark side of Tregs during aging
Open accessAbstract
In the last century, we have seen a dramatic rise in the number of older persons globally, a trend known as the grey (or silver) tsunami. People live markedly longer than their predecessors worldwide, due to remarkable changes in their lifestyle and in progresses made by modern medicine. However, the older we become, the more susceptible we are to a series of age-related pathologies, including infections, cancers, autoimmune diseases, and multi-morbidities. Therefore, a key challenge for our modern societies is how to cope with this fragile portion of the population, so that everybody could have the opportunity to live a long and healthy life. From a holistic point of view, aging results from the progressive decline of various systems. Among them, the distinctive age-dependent changes in the immune system contribute to the enhanced frailty of the elderly. One of these affects a population of lymphocytes, known as regulatory T cells (Tregs), as accumulating evidence suggest that there is a significant increase in the frequency of these cells in secondary lymphoid organs (SLOs) of aged animals. Although there are still discrepancies in the literature about modifications to their functional properties during aging, mounting evidence suggests a detrimental role for Tregs in the elderly in the context of bacterial and viral infections by suppressing immune responses against non-self-antigens. Interestingly, Tregs seem to also contribute to the reduced effectiveness of immunizations against many pathogens by limiting the production of vaccine-induced protective antibodies. In this review, we will analyze the current state of understandings about the role of Tregs in acute and chronic infections as well as in vaccination response in both humans and mice. Lastly, we provide an overview of current strategies for Treg modulation with potential future applications to improve the effectiveness of vaccines in older individuals.
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Age-associated B cells (ABCs; CD11c+T-bet+) and regulatory T cells (Tregs) are key regulators of immune tolerance in aging, and their expansion or loss, respectively, has been implicated in age-related autoimmunity and chronic inflammation.
“Age-associated B cells (ABCs; CD11c+T-bet+) and regulatory T cells (Tregs) are key regulators of immune tolerance in aging, and their expansion or loss, respectively, has been implicated in age-related autoimmunity and chronic inflammation [25–29].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [27]
The Introduction and Conclusion describe Tregs as regulators that restrain autoreactive responses, and the Conclusion says too few Tregs can lead to autoimmune responses. But the paper reports Treg accumulation with age, not a general loss, and the passages do not support the claim about expansion of CD11c+T-bet+ age-associated B cells or its link to chronic inflammation. (LLM, conf=0.88)
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- Authors
- Palatella, M., Guillaume, S. M., Linterman, M. A., & Huehn, J.
- Affiliations
- Helmholtz Centre for Infection Research (DE)
- Babraham Institute (GB)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Huehn, Jochen
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2022-08-09
- Volume
- 13
- Pages
- 940705-940705
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC9398463
- OpenAlex
- W4292451976
- Cited by
- 58
- References
- 239
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 14 · 2023: 8
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Horizon 2020 Framework Programme
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- regulatory T cells, aging, immunosenescence, vaccine response in the elderly, infection susceptibility, immunosuppression, secondary lymphoid organs, vaccine-induced antibodies, chronic infection, frailty
- MeSH terms
- Aged, Aged, 80 and over, Aging, Animals, Antibodies, Viral, Humans, Vaccination, Vaccines, T-Lymphocytes, Regulatory, Mice
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