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Published (Version of Record)CC BY-NC V4.0, Open Access
Journal article
Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis
The European respiratory journal, Vol.60(5), 2101469
2022
PMCID: PMC9684624
PMID: 35798357
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 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.
Details
- Title
- Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis
- Authors/Creators
- Cecilia M. Prele - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaTylah Miles - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaDavid R. Pearce - College Station Medical CenterRobert J. O'Donoghue - The University of MelbourneChris Grainge - College Station Medical CenterLucy Barrett - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaKimberly Birnie - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaAndrew D. Lucas - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaSvetlana Baltic - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaMatthias Ernst - Centro Universitário Newton PaivaCatherine Rinaldi - Univ Western Australia, Ctr Microscopy Characterisat & Anal, Nedlands, WA, AustraliaGeoffrey J. Laurent - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaDarryl A. Knight - Providence CollegeMark Fear - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaGerard Hoyne - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, AustraliaRobin J. McAnulty - College Station Medical CenterSteven E. Mutsaers - Univ Western Australia, Inst Resp Hlth, Nedlands, WA, Australia
- Publication Details
- The European respiratory journal, Vol.60(5), 2101469
- Publisher
- European Respiratory Society
- Number of pages
- 14
- Grant note
- 1067511 / British Lung Foundation PPRG15-10 / NHMRC project; National Health and Medical Research Council (NHMRC) of Australia Lung Foundation Australia Bill 1127337 / University of Western Australia Research TrainingPostgraduate Award National Health and Medical Research Council (NHMRC); National Health and Medical Research Council (NHMRC) of Australia
- Identifiers
- 991005634459807891
- Copyright
- ©The authors 2022.
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.208 Vasculitis & Autoimmune Disorders
- 1.208.1262 Idiopathic Pulmonary Fibrosis
- Web Of Science research areas
- Respiratory System
- ESI research areas
- Clinical Medicine