Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging
Age-related conditions, such as neurodegenerative disease, cancer, and autoimmune disorders, are increasingly recognized as closely linked with the gradual deterioration of the immune system. Regulatory T cells (Tregs) are a small, specialized subset of T lymphocytes that play a critical role in mai...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621759/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849418952607793152 |
|---|---|
| author | Lillie Lewis Deepa Valvi Roberto Gedaly Roberto Gedaly Roberto Gedaly Francesc Marti Francesc Marti Francesc Marti |
| author_facet | Lillie Lewis Deepa Valvi Roberto Gedaly Roberto Gedaly Roberto Gedaly Francesc Marti Francesc Marti Francesc Marti |
| author_sort | Lillie Lewis |
| collection | DOAJ |
| description | Age-related conditions, such as neurodegenerative disease, cancer, and autoimmune disorders, are increasingly recognized as closely linked with the gradual deterioration of the immune system. Regulatory T cells (Tregs) are a small, specialized subset of T lymphocytes that play a critical role in maintaining immune homeostasis and self-tolerance. As individuals age, Treg cells demonstrate reduced capacity to suppress some autoreactive immune responses, although they largely retain their capacity to regulate effector antiviral and antitumor immunity. Unlike conventional effector T cells (Teff), which primarily derive energy from glycolysis, Tregs rely more on mitochondrial oxidative phosphorylation to fulfill their energy requirements. This metabolic profile renders them particularly sensitive to mitochondrial dysfunction, underpinning the critical role of mitochondrial protective pathways in preserving the functional integrity of Treg cells. The mitochondrial unfolded protein response (mitoUPR) is gaining special relevance among these protective mechanisms. In this review, we examine the complex interplay between immune aging and mitochondrial dynamics, with particular emphasis on the essential role of mitoUPR in supporting Treg function. We further discuss how targeting mitochondrial stress responses may offer novel therapeutic avenues for age-related diseases characterized by Treg dysfunction. |
| format | Article |
| id | doaj-art-79360efc87a04f7287680d054e87ad81 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-79360efc87a04f7287680d054e87ad812025-08-20T03:32:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16217591621759Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune agingLillie Lewis0Deepa Valvi1Roberto Gedaly2Roberto Gedaly3Roberto Gedaly4Francesc Marti5Francesc Marti6Francesc Marti7Department of Surgery - Transplant Division, College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Surgery - Transplant Division, College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Surgery - Transplant Division, College of Medicine, University of Kentucky, Lexington, KY, United StatesLucillle Parker Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, United StatesAlliance Research Initiative (TILT Alliance), College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Surgery - Transplant Division, College of Medicine, University of Kentucky, Lexington, KY, United StatesLucillle Parker Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, United StatesAlliance Research Initiative (TILT Alliance), College of Medicine, University of Kentucky, Lexington, KY, United StatesAge-related conditions, such as neurodegenerative disease, cancer, and autoimmune disorders, are increasingly recognized as closely linked with the gradual deterioration of the immune system. Regulatory T cells (Tregs) are a small, specialized subset of T lymphocytes that play a critical role in maintaining immune homeostasis and self-tolerance. As individuals age, Treg cells demonstrate reduced capacity to suppress some autoreactive immune responses, although they largely retain their capacity to regulate effector antiviral and antitumor immunity. Unlike conventional effector T cells (Teff), which primarily derive energy from glycolysis, Tregs rely more on mitochondrial oxidative phosphorylation to fulfill their energy requirements. This metabolic profile renders them particularly sensitive to mitochondrial dysfunction, underpinning the critical role of mitochondrial protective pathways in preserving the functional integrity of Treg cells. The mitochondrial unfolded protein response (mitoUPR) is gaining special relevance among these protective mechanisms. In this review, we examine the complex interplay between immune aging and mitochondrial dynamics, with particular emphasis on the essential role of mitoUPR in supporting Treg function. We further discuss how targeting mitochondrial stress responses may offer novel therapeutic avenues for age-related diseases characterized by Treg dysfunction.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621759/fullregulatory T-cellscell metabolismcellular stressoxidative stressunfolded protein responseimmunosenescence |
| spellingShingle | Lillie Lewis Deepa Valvi Roberto Gedaly Roberto Gedaly Roberto Gedaly Francesc Marti Francesc Marti Francesc Marti Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging Frontiers in Immunology regulatory T-cells cell metabolism cellular stress oxidative stress unfolded protein response immunosenescence |
| title | Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging |
| title_full | Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging |
| title_fullStr | Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging |
| title_full_unstemmed | Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging |
| title_short | Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging |
| title_sort | mitochondrial unfolded protein response in regulatory t cell function a protective mechanism in immune aging |
| topic | regulatory T-cells cell metabolism cellular stress oxidative stress unfolded protein response immunosenescence |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621759/full |
| work_keys_str_mv | AT lillielewis mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT deepavalvi mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT robertogedaly mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT robertogedaly mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT robertogedaly mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT francescmarti mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT francescmarti mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging AT francescmarti mitochondrialunfoldedproteinresponseinregulatorytcellfunctionaprotectivemechanisminimmuneaging |