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

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

Title: Plasma cell but not CD20-mediated B cell depletion protects from bleomycin-induced lung fibrosis.
Creator: Prêle, Cecilia M.; Miles, Tylah; Rinaldi, Catherine; Laurent, Geoffrey J.; Knight, Darryl A.; Fear, Mark; Hoyne, Gerard; McAnulty, Robin J.; Mutsaers, Steven E.; Pearce, David R.; O'Donoghue, Robert J.; Grainge, Chris; Barrett, Lucy; Birnie, Kimberly; Lucas, Andrew D.; Baltic, Svetlana; Ernst, Matthias
Relation: European Respiratory Journal Vol. -, Issue 7 July 2022, no. 2101469
Publisher Link: http://dx.doi.org/10.1183/13993003.01469-2021
Publisher: European Respiratory Society
Resource Type: journal article
Date: 2022
Description: 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.
Subject: B cells; lung; transgenic/knockout mice; plasmablasts; plasma cells
Identifier: http://hdl.handle.net/1959.13/1465613
Identifier: uon:47318
Identifier: ISSN:0903-1936
Language: eng
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