Orai, STIM, and PMCA contribute to reduced calcium signal generation in CD8+ T cells of elderly mice.
Aging (Albany NY)
; 12(4): 3266-3286, 2020 02 12.
Article
en En
| MEDLINE
| ID: mdl-32062611
ABSTRACT
Ca2+ is a crucial second messenger for proper T cell function. Considering the relevance of Ca2+ signals for T cell functionality it is surprising that no mechanistic insights into T cell Ca2+ signals from elderly individuals are reported. The main Ca2+ entry mechanism in T cells are STIM-activated Orai channels. Their role during lymphocyte aging is completely unknown. Here, we report not only reduced Ca2+ signals in untouched and stimulated, but also in central and effector memory CD8+ T cells from elderly (18-24 months) compared to adult (3-6 months) mice. Two mechanisms contribute to the overall reduction in Ca2+ signals of CD8+ T cells of elderly mice 1) Reduced Ca2+ currents through Orai channels due to decreased expressions of STIMs and Orais. 2) A faster extrusion of Ca2+ owing to an increased expression of PMCA4. The reduced Ca2+ signals correlated with a resistance of the cytotoxic efficiency of CD8+ T cells to varying free [Ca2+]ext with age. In summary, reduced STIM/Orai expression and increased Ca2+ clearing rates following enhanced PMCA4 expression contribute to reduced Ca2+ signals in CD8+ T cells of elderly mice. These changes are apparently relevant to immune function as they reduce the Ca2+ dependency of CTL cytotoxicity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
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Linfocitos T CD8-positivos
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Señalización del Calcio
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ATPasas Transportadoras de Calcio de la Membrana Plasmática
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Molécula de Interacción Estromal 1
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Proteína ORAI1
Límite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania