TY - JOUR
T1 - Friend or foe
T2 - The dichotomous impact of T cells on neuro-de/ re-generation during aging
AU - Coder, Brandon
AU - Wang, Weikan
AU - Wang, Liefeng
AU - Wu, Zhongdao
AU - Zhuge, Qichuan
AU - Su, Dong Ming
N1 - Funding Information:
BC is supported by NIH/NIA USA, Training in the Neurobiology of Aging (T32AG020494). QZ is supported by National Natural Science Foundation of China (81371396). D-M.S is supported by NIH/NIAID USA (grant: R01AI121147)
PY - 2017
Y1 - 2017
N2 - The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/ or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neurodegeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymusinflammaging- neurodegeneration axis".
AB - The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/ or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neurodegeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymusinflammaging- neurodegeneration axis".
KW - Aging
KW - Immunotherapy
KW - Neurodegeneration
KW - T-cell immunity
UR - http://www.scopus.com/inward/record.url?scp=85010733381&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.12572
DO - 10.18632/oncotarget.12572
M3 - Review article
AN - SCOPUS:85010733381
SN - 1949-2553
VL - 8
SP - 7116
EP - 7137
JO - Oncotarget
JF - Oncotarget
IS - 4
ER -