When the Damage Is Done: Injury and Repair in Thymus Function
Even though the thymus is exquisitely sensitive to acute insults like infection, shock, or common cancer therapies such as cytoreductive chemo- or radiation-therapy, it also has a remarkable capacity for repair. This phenomenon of endogenous thymic regeneration has been known for longer even than it...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01745/full |
| _version_ | 1818245286745604096 |
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| author | Sinéad Kinsella Jarrod A. Dudakov Jarrod A. Dudakov Jarrod A. Dudakov |
| author_facet | Sinéad Kinsella Jarrod A. Dudakov Jarrod A. Dudakov Jarrod A. Dudakov |
| author_sort | Sinéad Kinsella |
| collection | DOAJ |
| description | Even though the thymus is exquisitely sensitive to acute insults like infection, shock, or common cancer therapies such as cytoreductive chemo- or radiation-therapy, it also has a remarkable capacity for repair. This phenomenon of endogenous thymic regeneration has been known for longer even than its primary function to generate T cells, however, the underlying mechanisms controlling the process have been largely unstudied. Although there is likely continual thymic involution and regeneration in response to stress and infection in otherwise healthy people, acute and profound thymic damage such as that caused by common cancer cytoreductive therapies or the conditioning regimes as part of hematopoietic cell transplantation (HCT), leads to prolonged T cell deficiency; precipitating high morbidity and mortality from opportunistic infections and may even facilitate cancer relapse. Furthermore, this capacity for regeneration declines with age as a function of thymic involution; which even at steady state leads to reduced capacity to respond to new pathogens, vaccines, and immunotherapy. Consequently, there is a real clinical need for strategies that can boost thymic function and enhance T cell immunity. One approach to the development of such therapies is to exploit the processes of endogenous thymic regeneration into novel pharmacologic strategies to boost T cell reconstitution in clinical settings of immune depletion such as HCT. In this review, we will highlight recent work that has revealed the mechanisms by which the thymus is capable of repairing itself and how this knowledge is being used to develop novel therapies to boost immune function. |
| first_indexed | 2024-12-12T14:30:30Z |
| format | Article |
| id | doaj.art-9f2c2a07ac0f4d26ac8127edf618e641 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T14:30:30Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9f2c2a07ac0f4d26ac8127edf618e6412022-12-22T00:21:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01745557241When the Damage Is Done: Injury and Repair in Thymus FunctionSinéad Kinsella0Jarrod A. Dudakov1Jarrod A. Dudakov2Jarrod A. Dudakov3Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United StatesProgram in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United StatesImmunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, United StatesDepartment of Immunology, University of Washington, Seattle, WA, United StatesEven though the thymus is exquisitely sensitive to acute insults like infection, shock, or common cancer therapies such as cytoreductive chemo- or radiation-therapy, it also has a remarkable capacity for repair. This phenomenon of endogenous thymic regeneration has been known for longer even than its primary function to generate T cells, however, the underlying mechanisms controlling the process have been largely unstudied. Although there is likely continual thymic involution and regeneration in response to stress and infection in otherwise healthy people, acute and profound thymic damage such as that caused by common cancer cytoreductive therapies or the conditioning regimes as part of hematopoietic cell transplantation (HCT), leads to prolonged T cell deficiency; precipitating high morbidity and mortality from opportunistic infections and may even facilitate cancer relapse. Furthermore, this capacity for regeneration declines with age as a function of thymic involution; which even at steady state leads to reduced capacity to respond to new pathogens, vaccines, and immunotherapy. Consequently, there is a real clinical need for strategies that can boost thymic function and enhance T cell immunity. One approach to the development of such therapies is to exploit the processes of endogenous thymic regeneration into novel pharmacologic strategies to boost T cell reconstitution in clinical settings of immune depletion such as HCT. In this review, we will highlight recent work that has revealed the mechanisms by which the thymus is capable of repairing itself and how this knowledge is being used to develop novel therapies to boost immune function.https://www.frontiersin.org/article/10.3389/fimmu.2020.01745/fullendogenous thymic regenerationimmune restorationT cell reconstitutionthymic epithelial cellsBMP4IL-22 |
| spellingShingle | Sinéad Kinsella Jarrod A. Dudakov Jarrod A. Dudakov Jarrod A. Dudakov When the Damage Is Done: Injury and Repair in Thymus Function Frontiers in Immunology endogenous thymic regeneration immune restoration T cell reconstitution thymic epithelial cells BMP4 IL-22 |
| title | When the Damage Is Done: Injury and Repair in Thymus Function |
| title_full | When the Damage Is Done: Injury and Repair in Thymus Function |
| title_fullStr | When the Damage Is Done: Injury and Repair in Thymus Function |
| title_full_unstemmed | When the Damage Is Done: Injury and Repair in Thymus Function |
| title_short | When the Damage Is Done: Injury and Repair in Thymus Function |
| title_sort | when the damage is done injury and repair in thymus function |
| topic | endogenous thymic regeneration immune restoration T cell reconstitution thymic epithelial cells BMP4 IL-22 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01745/full |
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