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Interleukin-10 expressing regulatory B cells are decreased in blood of smokers and COPD patients

Merel Jacobs, Sven Verschraegen, Bihiyga Salhi, Jasper Anckaert, Pieter Mestdagh, Guy Brusselle, Ken Bracke
ERJ Open Research 2022 8: 11; DOI: 10.1183/23120541.LSC-2022.11
Merel Jacobs
1Ghent University, Ghent, Belgium
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  • For correspondence: merel.jacobs@ugent.be
Sven Verschraegen
2Ghent University Hospital, Ghent, Belgium
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Bihiyga Salhi
2Ghent University Hospital, Ghent, Belgium
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Jasper Anckaert
1Ghent University, Ghent, Belgium
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Pieter Mestdagh
1Ghent University, Ghent, Belgium
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Guy Brusselle
1Ghent University, Ghent, Belgium
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Ken Bracke
1Ghent University, Ghent, Belgium
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Abstract

COPD is primarily caused by smoking and is characterized by chronic inflammation of the lungs leading to small airway obstruction and alveolar destruction (emphysema). A subset of B cells that suppresses immune responses through the release of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-b has been termed regulatory B cells (Bregs). Since Bregs are decreased and/or impaired in several (auto)-immune diseases we aimed to study IL-10+ Bregs in smokers and patients with COPD.

First, by immunohistochemical staining for CD20 and IL-10 we demonstrated the presence of IL-10 producing Bregs in human lung tissue. Next, we stimulated PBMCs from 9 never smokers, 8 smokers without airflow limitation and 13 patients with COPD GOLD stage I-IV for 48 hours with CpG/CD40L/PIB and observed a significantly lower percentage of IL-10+ Bregs within memory B cells from smokers and patients with COPD, compared to never smokers. Furthermore, IL-10 protein levels were reduced in culture supernatant of smokers and COPD patients and correlated significantly with the total percentage of IL-10+ Bregs. Addition of cigarette smoke extract (CSE) to in vitro cultured, PBMC-derived B cells significantly impaired their capacity to produce IL-10 in a concentration-dependent manner. Finally, gene expression levels of IL-10 promoting transcription factors IRF4 and HIF-1α were decreased in PBMC-derived memory B cells exposed in vitro to CSE.

In conclusion, reduced Breg numbers and function in smokers and patients with COPD might contribute to the initiation and progression of the disease. These observations could have important implications for future therapies targeting B cells in COPD.

  • COPD - mechanism
  • Immunology
  • Anti-inflammatory

Footnotes

Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 11.

This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.

This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2022
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Interleukin-10 expressing regulatory B cells are decreased in blood of smokers and COPD patients
Merel Jacobs, Sven Verschraegen, Bihiyga Salhi, Jasper Anckaert, Pieter Mestdagh, Guy Brusselle, Ken Bracke
ERJ Open Research Mar 2022, 8 (suppl 8) 11; DOI: 10.1183/23120541.LSC-2022.11

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Interleukin-10 expressing regulatory B cells are decreased in blood of smokers and COPD patients
Merel Jacobs, Sven Verschraegen, Bihiyga Salhi, Jasper Anckaert, Pieter Mestdagh, Guy Brusselle, Ken Bracke
ERJ Open Research Mar 2022, 8 (suppl 8) 11; DOI: 10.1183/23120541.LSC-2022.11
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