B Cell Depletion Inhibits Fibrosis via Suppression of Profibrotic Macrophage Differentiation in a Mouse Model of Systemic Sclerosis.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
09
05
2020
accepted:
25
04
2021
pubmed:
7
5
2021
medline:
16
12
2021
entrez:
6
5
2021
Statut:
ppublish
Résumé
We undertook this study to investigate the effect of B cell depletion on fibrosis in systemic sclerosis (SSc) and its mechanism of action. Mice with bleomycin-induced SSc (BLM-SSc) were treated with anti-CD20 antibody, and skin and lung fibrosis were histopathologically evaluated. T cells and macrophages were cocultured with B cells, and the effect of B cells on their differentiation was assessed by flow cytometry. We also cocultured B cells and monocytes from SSc patients and analyzed the correlation between fibrosis and profibrotic macrophage induction by B cells. B cell depletion inhibited fibrosis in mice with BLM-SSc. B cells from mice with BLM-SSc increased proinflammatory cytokine-producing T cells in coculture. In mice with BLM-SSc, B cell depletion before BLM treatment (pre-depletion) inhibited fibrosis more strongly than B cell depletion after BLM treatment (post-depletion) (P < 0.01). However, the frequencies of proinflammatory T cells were lower in the post-depletion group than in the pre-depletion group. This discrepancy suggests that the effect of B cell depletion on fibrosis cannot be explained by its effect on T cell differentiation. On the other hand, profibrotic macrophages were markedly decreased in the pre-depletion group compared to the post-depletion group (P < 0.05). Furthermore, B cells from mice with BLM-SSc increased profibrotic macrophage differentiation in coculture (P < 0.05). In SSc patients, the extent of profibrotic macrophage induction by B cells correlated with the severity of fibrosis (P < 0.0005). These findings suggest that B cell depletion inhibits tissue fibrosis via suppression of profibrotic macrophage differentiation in mice with BLM-SSc, providing a new rationale for B cell depletion therapy in SSc.
Substances chimiques
Bleomycin
11056-06-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2086-2095Informations de copyright
© 2021, American College of Rheumatology.
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