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Physiol Rep. 2016 Dec;4(24). pii: e13057. doi: 10.14814/phy2.13057.

Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice.

Author information

1
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
2
State Key Laboratory of Respiratory Disease, and Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
3
Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.
4
Centre de Recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
5
Department of Medicine & Center for Heart Lung Innovation, University of British Columbia St. Paul's Hospital, Vancouver, Canada.
6
Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
7
Department of Pathology & Medical Biology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
8
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York.
9
Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
10
Department of Molecular Medicine, Laval University, Québec, Canada.
11
MedImmune LLC, Gaithersburg, Maryland.
12
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada stampfli@mcmaster.ca.
13
Department of Medicine, Firestone Institute of Respiratory Health at St. Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.

Abstract

Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking.

KEYWORDS:

BAFF ; COPD ; Animal model; autoantibodies; cigarette smoke

PMID:
28039405
PMCID:
PMC5210376
DOI:
10.14814/phy2.13057
[Indexed for MEDLINE]
Free PMC Article

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