Domino Effect of Interleukin-15 and CD8 T-Cell–Mediated Neuronal Apoptosis in Experimental Traumatic Brain Injury
| Autor: | Rong Hua, Ning-Ning Ji, Pan-Pan Chen, Yong-Mei Zhang, Liang Wu, Guo-Lin Sun, Jing-Yu Hua, Hang Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
030506 rehabilitation Traumatic brain injury medicine.medical_treatment Central nervous system Apoptosis CD8-Positive T-Lymphocytes 03 medical and health sciences 0302 clinical medicine Immune system Brain Injuries Traumatic medicine Animals Cytotoxic T cell Rats Wistar Interleukin-15 Neurons business.industry Interleukin medicine.disease Rats Disease Models Animal medicine.anatomical_structure Cytokine Interleukin 15 Cancer research Neurology (clinical) 0305 other medical science business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurotrauma. 38:1450-1463 |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | The effects of local factors on activation of immune cells infiltrating the central nervous system (CNS) in a rat model of traumatic brain injury (TBI) remain elusive. The cytokine, interleukin (IL)-15, is crucial for development and activation of CD8 T lymphocytes, a prominent lymphocytic population present in TBI lesions. We investigated whether IL-15 originates from astrocytes and whether IL-15 can evoke the CD8 T-lymphocyte response in TBI. We observed that astrocytes were activated in a rat model of TBI and that IL-15 was overexpressed on the surface of astrocytes. Further, CD8 T lymphocytes infiltrating TBI lesions colocalized with IL-15-expressing astrocytes. Activated CD8 T lymphocytes released granzyme B (Gra-b), which, in turn, activated caspase-3-induced poly(ADP-ribose) polymerase cleavage and, ultimately, neuronal apoptosis. Conversely, inhibition of astrocyte activation by pre-treatment with the specific inhibitor, fluorocitrate (FC), that reduces carbon flux through the Krebs cycle in astrocytes resulted in improved neurological function and memory. FC pre-treatment was also associated with downregulated IL-15 expression and CD8 T-cell activation as well as decreased levels of neuronal apoptosis, suggesting that IL-15 initiated a domino effect toward apoptosis. In contrast, rats pre-treated with recombinant rat IL-15 showed upregulated CD8 T-cell numbers and Gra-b levels, in addition to induction of neuronal apoptosis. Together, our results indicated that IL-15 could induce neuronal apoptosis by enhancing CD8 T-cell function in a rat model of TBI. |
| Databáze: | OpenAIRE |
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