RT Journal Article
SR Electronic
T1 Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2101469
DO 10.1183/13993003.01469-2021
VO 60
IS 5
A1 Cecilia M. Prêle
A1 Tylah Miles
A1 David R. Pearce
A1 Robert J. O'Donoghue
A1 Chris Grainge
A1 Lucy Barrett
A1 Kimberly Birnie
A1 Andrew D. Lucas
A1 Svetlana Baltic
A1 Matthias Ernst
A1 Catherine Rinaldi
A1 Geoffrey J. Laurent
A1 Darryl A. Knight
A1 Mark Fear
A1 Gerard Hoyne
A1 Robin J. McAnulty
A1 Steven E. Mutsaers
YR 2022
UL http://erj.ersjournals.com/content/60/5/2101469.abstract
AB 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.Bortezomib-mediated depletion of plasma cells but not anti-CD20-mediated B-cell depletion inhibited bleomycin-induced lung fibrosis, suggesting that plasma cells are a therapeutic target for fibrotic lung disease such as IPF. https://bit.ly/3Nv4w5P