CLEC16A regulates splenocyte and NK cell function in part through MEK signaling.
PLoS One
; 13(9): e0203952, 2018.
Article
en En
| MEDLINE
| ID: mdl-30226884
ABSTRACT
CLEC16A is implicated in multiple autoimmune diseases. We generated Clec16a inducible knockout (KO) mice to examine the functional link between CLEC16A auto-inflammation and autoimmunity. Clec16a KO mice exhibited weight loss and thymic and splenic atrophy. Mitochondrial potential was lowered in KO mice splenocytes resulting in aggregation of unhealthy mitochondria in B, T, and NK cells. In Clec16a KO mice we detected disrupted mitophagy in splenic B and T cells. NK cells from Clec16a KO mice exhibited increased cytotoxicity. Incomplete mitophagy was attenuated with PI3K and/or MEK inhibition in Clec16a KO mice. Our results demonstrate a functional link between CLEC16A and disrupted mitophagy in immune cells and show that incomplete mitophagy predisposes the KO mice to inflammation. Taken together, loss of function variants in CLEC16A that are associated with decreased CLEC16A expression levels may contribute to inflammation in autoimmunity through disrupted mitophagy. Drugs modulating mitophagy reverse the process and may be effective in treating and preventing autoimmunity in individuals with risk associated CLEC16A variants.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Bazo
/
Proteínas de Transporte de Monosacáridos
/
Células Asesinas Naturales
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Sistema de Señalización de MAP Quinasas
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Lectinas Tipo C
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos