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

Benkhoucha, Mahdia; Ngoc, Lan Tran; Breville, Gautier; Senoner, Isis; Bradfield, Paul F.; Papayannopoulou, Thalia; Merkler, Doron; Korn, Thomas und Lalive, Patrice H. (2022): CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation. In: Journal of Neuroinflammation, Bd. 19, Nr. 1, 103

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 alpha 4 (Itg alpha 4). The adoptive transfer of Itg alpha 4-expressing CD4(+)V alpha 3.2(+)c-Met(+) T cells induces increased disease severity compared to CD4(+)V alpha 3.2(+)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 Itg alpha 4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4(+) T lymphocytes associated with neuroinflammation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198