B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis.
Cell Rep Med
; 5(1): 101351, 2024 01 16.
Article
em En
| MEDLINE
| ID: mdl-38134930
ABSTRACT
Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Whereas T cells are likely the main drivers of disease development, the striking efficacy of B cell-depleting therapies (BCDTs) underscore B cells' involvement in disease progression. How B cells contribute to multiple sclerosis (MS) pathogenesis-and consequently the precise mechanism of action of BCDTs-remains elusive. Here, we analyze the impact of BCDTs on the immune landscape in patients with MS using high-dimensional single-cell immunophenotyping. Algorithm-guided analysis reveals a decrease in circulating T follicular helper-like (Tfh-like) cells alongside increases in CD27 expression in memory T helper cells and Tfh-like cells. Elevated CD27 indicates disrupted CD27/CD70 signaling, as sustained CD27 activation in T cells leads to its cleavage. Immunohistological analysis shows CD70-expressing B cells at MS lesion sites. These results suggest that the efficacy of BCDTs may partly hinge upon the disruption of Th cell and B cell interactions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Múltipla
Limite:
Humans
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça
País de publicação:
Estados Unidos