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Scientific article
Open access
English

CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation

Published inJournal of neuroinflammation, vol. 19, no. 1, 103
Publication date2022-04-29
First online date2022-04-29
Abstract

Objective: c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4+c-Met+T cells are detected at increased levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS).

Methods: c-Met expression by CD4+T cells was analyzed mostly by flow cytometry and by immunohistochemistry from mice and human PBMCs. The in vivo role of CD4+c-Met+T cells was assessed in EAE.

Results: CD4+c-Met+T cells found in the CNS during EAE peak disease are characterized by a pro-inflammatory phenotype skewed towards a Th1 and Th17 polarization, with enhanced adhesion and transmigration capacities correlating with increased expression of integrin α4 (Itgα4). The adoptive transfer of Itgα4-expressing CD4+Vα3.2+c-Met+T cells induces increased disease severity compared to CD4+Vα3.2+c-Met-T cells. Finally, CD4+c-Met+T cells are detected in the brain of MS patients, as well as in the blood with a higher level of Itgα4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4+T lymphocytes associated with neuroinflammation.

eng
Keywords
  • EAE
  • HGF
  • Integrin
  • MS
  • Neuroinflammation
  • T lymphocytes
  • Transmigration
  • C-Met
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Integrin alpha4
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / pathology
  • Neuroinflammatory Diseases
  • Th17 Cells
Citation (ISO format)
BENKHOUCHA, Mahdia et al. CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation. In: Journal of neuroinflammation, 2022, vol. 19, n° 1, p. 103. doi: 10.1186/s12974-022-02461-7
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Identifiers
ISSN of the journal1742-2094
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