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Autotaxin in encephalitogenic CD4 T cells as a therapeutic target for multiple sclerosis.
Petersen-Cherubini, Cora L; Murphy, Shawn P; Xin, Matthew; Liu, Yue; Deffenbaugh, Joshua L; Jahan, Ishrat; Rau, Christina N; Yang, Yuhong; Lovett-Racke, Amy E.
Afiliação
  • Petersen-Cherubini CL; Neuroscience Graduate Program, The Ohio State University, Columbus, Ohio, USA.
  • Murphy SP; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Xin M; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Liu Y; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Deffenbaugh JL; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Jahan I; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Rau CN; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Yang Y; Department of Microbial Infection and Immunity, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
  • Lovett-Racke AE; Department of Neurology, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
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.
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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

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