CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury
Despite the advances in therapeutic interventions, solid organ transplantation (SOT) remains the “gold standard” treatment for patients with end-stage organ failure. Recently, vascularized composite allotransplantation (VCA) has reemerged as a feasible treatment option for patients with complex comp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1270300/full |
| _version_ | 1797665277672947712 |
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| author | Shareni Jeyamogan Joseph R. Leventhal Joseph R. Leventhal James M. Mathew James M. Mathew James M. Mathew Zheng Jenny Zhang Zheng Jenny Zhang Zheng Jenny Zhang |
| author_facet | Shareni Jeyamogan Joseph R. Leventhal Joseph R. Leventhal James M. Mathew James M. Mathew James M. Mathew Zheng Jenny Zhang Zheng Jenny Zhang Zheng Jenny Zhang |
| author_sort | Shareni Jeyamogan |
| collection | DOAJ |
| description | Despite the advances in therapeutic interventions, solid organ transplantation (SOT) remains the “gold standard” treatment for patients with end-stage organ failure. Recently, vascularized composite allotransplantation (VCA) has reemerged as a feasible treatment option for patients with complex composite tissue defects. In both SOT and VCA, ischemia reperfusion injury (IRI) is inevitable and is a predominant factor that can adversely affect transplant outcome by potentiating early graft dysfunction and/or graft rejection. Restoration of oxygenated blood supply to an organ which was previously hypoxic or ischemic for a period of time triggers cellular oxidative stress, production of both, pro-inflammatory cytokines and chemokines, infiltration of innate immune cells and amplifies adaptive alloimmune responses in the affected allograft. Currently, Food and Drug Administration (FDA) approved drugs for the treatment of IRI are unavailable, therefore an efficacious therapeutic modality to prevent, reduce and/or alleviate allograft damages caused by IRI induced inflammation is warranted to achieve the best-possible transplant outcome among recipients. The tolerogenic capacity of CD4+CD25+FOXP3+ regulatory T cells (Tregs), have been extensively studied in the context of transplant rejection, autoimmunity, and cancer. It was not until recently that Tregs have been recognized as a potential cell therapeutic candidate to be exploited for the prevention and/or treatment of IRI, owing to their immunomodulatory potential. Tregs can mitigate cellular oxidative stress, produce anti-inflammatory cytokines, promote wound healing, and tissue repair and prevent the infiltration of pro-inflammatory immune cells in injured tissues. By using strategic approaches to increase the number of Tregs and to promote targeted delivery, the outcome of SOT and VCA can be improved. This review focuses on two sections: (a) the therapeutic potential of Tregs in preventing and mitigating IRI in the context of SOT and VCA and (b) novel strategies on how Tregs could be utilized for the prevention and/or treatment of IRI. |
| first_indexed | 2024-03-11T19:42:38Z |
| format | Article |
| id | doaj.art-93810d6469bf4b8e87a41b24fc729752 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T19:42:38Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-93810d6469bf4b8e87a41b24fc7297522023-10-06T07:56:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12703001270300CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injuryShareni Jeyamogan0Joseph R. Leventhal1Joseph R. Leventhal2James M. Mathew3James M. Mathew4James M. Mathew5Zheng Jenny Zhang6Zheng Jenny Zhang7Zheng Jenny Zhang8Department of Surgery, Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Surgery, Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Surgery, Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDepartment of Surgery, Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesMicrosurgery and Pre-Clinical Research Core, Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDespite the advances in therapeutic interventions, solid organ transplantation (SOT) remains the “gold standard” treatment for patients with end-stage organ failure. Recently, vascularized composite allotransplantation (VCA) has reemerged as a feasible treatment option for patients with complex composite tissue defects. In both SOT and VCA, ischemia reperfusion injury (IRI) is inevitable and is a predominant factor that can adversely affect transplant outcome by potentiating early graft dysfunction and/or graft rejection. Restoration of oxygenated blood supply to an organ which was previously hypoxic or ischemic for a period of time triggers cellular oxidative stress, production of both, pro-inflammatory cytokines and chemokines, infiltration of innate immune cells and amplifies adaptive alloimmune responses in the affected allograft. Currently, Food and Drug Administration (FDA) approved drugs for the treatment of IRI are unavailable, therefore an efficacious therapeutic modality to prevent, reduce and/or alleviate allograft damages caused by IRI induced inflammation is warranted to achieve the best-possible transplant outcome among recipients. The tolerogenic capacity of CD4+CD25+FOXP3+ regulatory T cells (Tregs), have been extensively studied in the context of transplant rejection, autoimmunity, and cancer. It was not until recently that Tregs have been recognized as a potential cell therapeutic candidate to be exploited for the prevention and/or treatment of IRI, owing to their immunomodulatory potential. Tregs can mitigate cellular oxidative stress, produce anti-inflammatory cytokines, promote wound healing, and tissue repair and prevent the infiltration of pro-inflammatory immune cells in injured tissues. By using strategic approaches to increase the number of Tregs and to promote targeted delivery, the outcome of SOT and VCA can be improved. This review focuses on two sections: (a) the therapeutic potential of Tregs in preventing and mitigating IRI in the context of SOT and VCA and (b) novel strategies on how Tregs could be utilized for the prevention and/or treatment of IRI.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1270300/fullischemiareperfusionregulatory T cellsanti-inflammationoxidative stressallografts |
| spellingShingle | Shareni Jeyamogan Joseph R. Leventhal Joseph R. Leventhal James M. Mathew James M. Mathew James M. Mathew Zheng Jenny Zhang Zheng Jenny Zhang Zheng Jenny Zhang CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury Frontiers in Immunology ischemia reperfusion regulatory T cells anti-inflammation oxidative stress allografts |
| title | CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury |
| title_full | CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury |
| title_fullStr | CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury |
| title_full_unstemmed | CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury |
| title_short | CD4+CD25+FOXP3+ regulatory T cells: a potential “armor” to shield “transplanted allografts” in the war against ischemia reperfusion injury |
| title_sort | cd4 cd25 foxp3 regulatory t cells a potential armor to shield transplanted allografts in the war against ischemia reperfusion injury |
| topic | ischemia reperfusion regulatory T cells anti-inflammation oxidative stress allografts |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1270300/full |
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