Autotaxin in encephalitogenic CD4 T cells as a therapeutic target for multiple sclerosis.
Eur J Immunol
; 54(1): e2350561, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-37850588
ABSTRACT
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the CNS. A defining characteristic of MS is the ability of autoreactive T lymphocytes to cross the blood-brain barrier and mediate inflammation within the CNS. Previous work from our lab found the gene Enpp2 to be highly upregulated in murine encephalitogenic T cells. Enpp2 encodes for the protein autotaxin, a secreted glycoprotein that catalyzes the production of lysophosphatidic acid and promotes transendothelial migration of T cells from the bloodstream into the lymphatic system. The present study sought to characterize autotaxin expression in T cells during CNS autoimmune disease and determine its potential therapeutic value. Myelin-activated CD4 T cells upregulated expression of autotaxin in vitro, and ex vivo analysis of CNS-infiltrating CD4 T cells showed significantly higher autotaxin expression compared with cells from healthy mice. In addition, inhibiting autotaxin in myelin-specific T cells reduced their encephalitogenicity in adoptive transfer studies and decreased in vitro cell motility. Importantly, using two mouse models of MS, treatment with an autotaxin inhibitor ameliorated EAE severity, decreased the number of CNS infiltrating T and B cells, and suppressed relapses, suggesting autotaxin may be a promising therapeutic target in the treatment of MS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encefalomielite Autoimune Experimental
/
Esclerose Múltipla
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos