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Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

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posted on 2023-07-27, 06:18 authored by CM Prêle, T Miles, DR Pearce, RJ O’Donoghue, C Grainge, L Barrett, K Birnie, AD Lucas, S Baltic, Matthias ErnstMatthias Ernst, C Rinaldi, GJ Laurent, DA Knight, M Fear, G Hoyne, RJ McAnulty, SE Mutsaers
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+ CD138+ plasma cells. Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

Funding

This work is funded by National Health and Medical Research Council (NHMRC) project grant #1067511 and British Lung Foundation Grant PPRG15-10. C.M. Prêle, M. Fear and S.E. Mutsaers are supported by NHMRC project grant #1127337. T. Miles is supported by a University of Western Australia Research Training Postgraduate Award and the Lung Foundation Australia Bill van Nierop PhD Scholarship.

History

Publication Date

2022-11-24

Journal

European Respiratory Journal

Volume

60

Issue

5

Article Number

2101469

Pagination

14p.

Publisher

European Respiratory Society

ISSN

0903-1936

Rights Statement

©The authors 2022. This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

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