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

Cecilia M Prêle, Tylah Miles, David R Pearce, Robert J O'Donoghue, Chris Grainge, Lucy Barrett, Kimberly Birnie, Andrew D Lucas, Svetlana Baltic, Matthias Ernst, Catherine Rinaldi, Geoffrey J Laurent, Darryl A Knight, Mark Fear, Gerard Hoyne, Robin J McAnulty, Steven E Mutsaers

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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 previously shown 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 (PCs). 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 PCs, reduced the level of Blm-induced lung fibrosis, implicating PCs as important effector cells in the development and progression of pulmonary fibrosis.
Original languageEnglish
Article number2101469
JournalThe European Respiratory Journal
Volume60
Issue number5
Early online date7 Jul 2022
DOIs
Publication statusPublished - 1 Nov 2022

Fingerprint

Dive into the research topics of 'Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis'. Together they form a unique fingerprint.

Cite this