VISTA regulates microglia homeostasis and myelin phagocytosis, and is associated with MS lesion pathology.
Acta Neuropathol Commun
; 9(1): 91, 2021 05 18.
Article
en En
| MEDLINE
| ID: mdl-34006329
ABSTRACT
V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator (NCR) that is involved in T-cell quiescence, inhibition of T-cell activation, and in myeloid cells regulates cytokine production, chemotaxis, phagocytosis, and tolerance induction. In the central nervous system (CNS), VISTA is expressed by microglia, the resident macrophage of the parenchyma, and expression is decreased during neuroinflammation; however, the function of VISTA in microglia is unknown. Here, we extensively analyzed VISTA expression in different MS lesion stages and characterized the function of VISTA in the CNS by deleting VISTA in microglia. VISTA is differentially expressed in distinct MS lesion stages. In mice, VISTA deletion in Cx3Cr1-expressing cells induced a more amoeboid microglia morphology, indicating an immune-activated phenotype. Expression of genes associated with cell cycle and immune-activation was increased in VISTA KO microglia. In response to LPS and during experimental autoimmune encephalomyelitis (EAE), VISTA KO and WT microglia shared similar transcriptional profiles and VISTA deletion did not affect EAE disease progression or microglia responses. VISTA KO in microglia in vitro decreased the uptake of myelin. This study demonstrates that VISTA is involved in microglia function, which likely affects healthy CNS homeostasis and neuroinflammation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fagocitosis
/
Microglía
/
Homeostasis
/
Proteínas de la Membrana
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Esclerosis Múltiple
/
Vaina de Mielina
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Países Bajos