: 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.

B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis / Ulutekin, Can; Galli, Edoardo; Schreiner, Bettina; Khademi, Mohsen; Callegari, Ilaria; Piehl, Fredrik; Sanderson, Nicholas; Kirschenbaum, Daniel; Mundt, Sarah; Filippi, Massimo; Furlan, Roberto; Olsson, Tomas; Derfuss, Tobias; Ingelfinger, Florian; Becher, Burkhard. - In: CELL REPORTS MEDICINE. - ISSN 2666-3791. - 5:1(2024). [10.1016/j.xcrm.2023.101351]

B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis

Filippi, Massimo;Furlan, Roberto;
2024-01-01

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.
2024
B cell depletion
CD27
CD4(+) T cells
CD70
mass cytometry
multiple sclerosis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/155178
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