Prêle, Cecilia M;
Miles, Tylah;
Pearce, David R;
O'Donoghue, Robert J;
Grainge, Chris;
Barrett, Lucy;
Birnie, Kimberly;
... Mutsaers, Steven E; + view all
(2022)
Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis.
European Respiratory Journal
, 60
(5)
, Article 2101469. 10.1183/13993003.01469-2021.
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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.
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