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The role of T cells in age-related diseases

Subjects

Abstract

Age-related T cell dysfunction can lead to failure of immune tolerance mechanisms, resulting in aberrant T cell-driven cytokine and cytotoxic responses that ultimately cause tissue damage. In this Review, we discuss the role of T cells in the onset and progression of age-associated conditions, focusing on cardiovascular disorders, metabolic dysfunction, neuroinflammation and defective tissue repair and regeneration. We present different mechanisms by which T cells contribute to inflammageing and might act as modulators of age-associated diseases, including through enhanced pro-inflammatory and cytotoxic activity, defective clearance of senescent cells or regulation of the gut microbiota. Finally, we propose that ‘resetting’ immune system tolerance or targeting pathogenic T cells could open up new therapeutic opportunities to boost resilience to age-related diseases.

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Fig. 1: Molecular basis of T cell contribution to inflammageing and age-related diseases.
Fig. 2: T cell contribution to atherosclerosis.
Fig. 3: T cell contribution to adipose tissue inflammation and pathology in obesity and ageing.
Fig. 4: T cells participate in age-related neurological disorders.
Fig. 5: T cell control of gut homeostasis is lost during ageing, driving inflammatory pathologies.
Fig. 6: T cell based-immunotherapies to increase resilience to age-related diseases.

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Acknowledgements

The authors thank M. N. Navarro and G. Soto-Heredero for helpful comments on the manuscript. This study was supported by the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI19/855), the European Regional Development Fund (ERDF) and the European Commission through H2020-EU.1.1, European Research Council grant ERC-2016-StG 715322-EndoMitTalk and the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with Universidad Autónoma de Madrid in the line of action encouraging youth research doctors, in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) (SI1/PJI/2019-00073). M.M. is supported by the Miguel Servet Program (CP 19/014, Fundación de Investigación del Hospital 12 de Octubre). M.M.G.H. and E.G.-R. are supported by an FPU grant (FPU19/02576) and a Juan de la Cierva grant (IJC2018-036850-I), respectively, both from Ministerio de Ciencia, Innovación y Universidades (Spain).

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All authors substantially contributed to this work. Conceptualization: M.M., E.C. and G.D.-M.; writing — original draft preparation: E.C., E.G.-R., M.M.G.H., G.D.-M., J.F.A. and M.M.; preparation of figures: M.M.G.H.; review and editing: E.C., E.G.-R., M.M.G.H. and M.M.

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Correspondence to Maria Mittelbrunn.

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Nature Reviews Immunology thanks D. Winer and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

T effector memory CD45RA+ (TEMRA) cells

A subset of human memory T cells. TEMRA cells re-express the naive T cell-associated marker CD45RA and display multiple characteristics associated with senescence.

Inflammageing

Low-grade chronic inflammation in the absence of infection that appears in association with ageing.

Senescence-associated secretory phenotype

(SASP). Cellular response associated with the irreversible arrest of cell proliferation and consisting of the release of cytokines, chemokines, proteases and growth factors that affect nearby cells in a paracrine manner.

Senescence surveillance

Immune-mediated clearance of senescent cells.

Dysbiosis

Abnormal shifts in the microbiota composition and in the associated microbiota-derived metabolites.

Bacterial translocation

The leakage of viable bacteria and/or their by-products from the intestinal lumen to peripheral tissues, such as the mesenteric lymph nodes, the adipose tissue or the liver.

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Carrasco, E., Gómez de las Heras, M.M., Gabandé-Rodríguez, E. et al. The role of T cells in age-related diseases. Nat Rev Immunol (2021). https://doi.org/10.1038/s41577-021-00557-4

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