Mutation of an L-Type Calcium Channel Gene Leads to T Lymphocyte Dysfunction.
Front Immunol
; 10: 2473, 2019.
Article
em En
| MEDLINE
| ID: mdl-31736943
ABSTRACT
Calcium (Ca2+) is a vital secondary messenger in T lymphocytes regulating a vast array of important events including maturation, homeostasis, activation, and apoptosis and can enter the cell through CRAC, TRP, and CaV channels. Here we describe a mutation in the L-type Ca2+ channel CaV1.4 leading to T lymphocyte dysfunction, including several hallmarks of immunological exhaustion. CaV1.4-deficient mice exhibited an expansion of central and effector memory T lymphocytes, and an upregulation of inhibitory receptors on several T cell subsets. Moreover, the sustained elevated levels of activation markers on B lymphocytes suggest that they are in a chronic state of activation. Functionally, T lymphocytes exhibited a reduced store-operated Ca2+ flux compared to wild-type controls. Finally, modifying environmental conditions by herpes virus infection exacerbated the dysfunctional immune phenotype of the CaV1.4-deficient mice. This is the first example where the mutation of a CaV channel leads to T lymphocyte dysfunction, including the upregulation of several inhibitory receptors, hallmarks of T cell exhaustion, and establishes the physiological importance of CaV channel signaling in maintaining a nimble immune system.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Linfócitos T
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Canais de Cálcio Tipo L
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2019
Tipo de documento:
Article