IL-10 producing regulatory B cells are decreased in blood from smokers and COPD patients

Merel Jacobs, Sven Verschraegen, Bihiyga Salhi, Jasper Anckaert, Pieter Mestdagh, Guy G. Brusselle, Ken R. Bracke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Downloads (Pure)

Abstract

Background: Two opposing B cell subsets have been defined based on their cytokine profile: IL-6 producing effector B cells (B-effs) versus IL-10 producing regulatory B cells (B-regs) that respectively positively or negatively regulate immune responses. B-regs are decreased and/or impaired in many autoimmune diseases and inflammatory conditions. Since there is increasing evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD, the aim of this study was to investigate the presence and function of B-regs in COPD. Methods: First, presence of IL-10 producing regulatory B cells in human lung tissue was determined by immunohistochemistry. Secondly, quantification of IL-10 + B-regs and IL-6 + B-effs in peripheral blood mononuclear cells (PBMCs) from healthy controls, smokers without airflow limitation, and COPD patients (GOLD stage I-IV) was performed by flow cytometry. Thirdly, we exposed blood-derived B cells from COPD patients in vitro to cigarette smoke extract (CSE) and quantified IL-10 + B-regs and IL-6 + B-effs. Furthermore, we aimed at restoring the perturbed IL10 production by blocking BAFF. Fourthly, we determined mRNA expression of transcription factors involved in IL-10 production in FACS sorted memory- and naive B cells upon exposure to medium or CSE. Results: The presence of IL-10 producing regulatory B cells in parenchyma and lymphoid follicles in lungs was confirmed by immunohistochemistry. The percentage of IL-10 + B-regs was significantly decreased in blood-derived memory B cell subsets from smokers without airflow limitation and patients with COPD, compared to never smokers. Furthermore, the capacity of B cells to produce IL-10 was reduced upon in vitro exposure to CSE and this could not be restored by BAFF-blockade. Finally, upon CSE exposure, mRNA levels of the transcription factors IRF4 and HIF-1α, were decreased in memory B cells. Conclusion: Decreased numbers and impaired function of B-regs in smokers and patients with COPD might contribute to the initiation and progression of the disease.

Original languageEnglish
Article number287
JournalRespiratory Research
Volume23
Issue number1
DOIs
Publication statusPublished - 17 Oct 2022

Bibliographical note

Funding Information:
The research described in this article was supported by the Concerted Research Action of the Ghent University (BOF/GOA 01G00819) and by the Fund for Scientific Research in Flanders (FWO Vlaanderen, G052518N and 3G037618, and EOS‐contract G0G2318N). KRB holds an AstraZeneca Chair on Translational Research into the Pathogenesis of COPD.

Publisher Copyright: © 2022, The Author(s).

Fingerprint

Dive into the research topics of 'IL-10 producing regulatory B cells are decreased in blood from smokers and COPD patients'. Together they form a unique fingerprint.

Cite this