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

• Published in: Physiological reports 2016-12, Vol.4 (24), p.np-n/a
• Main Authors: Morissette, Mathieu C., Gao, Yang, Shen, Pamela, Thayaparan, Danya, Bérubé, Jean‐Christophe, Paré, Peter D., Brandsma, Corry‐Anke, Hao, Ke, Bossé, Yohan, Ettinger, Rachel, Herbst, Ronald, Humbles, Alison A., Kolbeck, Roland, Zhong, Nanshan, Chen, Rongchang, Stämpfli, Martin R.
• Format: Article
• Language: English
• Subjects: Alveoli; Animal model; Animals; Antibodies, Antinuclear - metabolism; Antinuclear antibodies; Autoantibodies; B-Cell Activating Factor - immunology; B-Cell Activating Factor - metabolism; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; BAFF; BLyS protein; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Cigarette Smoking - adverse effects; Cigarettes; COPD; Drug addiction; Fc receptors; Female; Females; Gene expression; Humans; Immune system; Immunoglobulin M - metabolism; Immunology; Inflammation; Investigations; Lung; Lung - drug effects; Lung - immunology; Lung - metabolism; Lung diseases; Lungs; Lymphocytes B; Lymphoid tissue; Macrophages; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neutrophilia; Nicotiana - adverse effects; Obstructive lung disease; Original Research; Pathogenesis; Physiology; Proteins; Respiratory Conditions Disorder and Diseases; Smoking Cessation; Spleen - drug effects; Spleen - metabolism; Tertiary Lymphoid Structures - chemically induced; Tertiary Lymphoid Structures - immunology; Tobacco smoke; Toxins, Pollutants and Chemical Agents
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.13057

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. This study shows a central role of BAFF in the induction and maintenance of cigarette smoke‐induced pulmonary antinuclear antibodies (ANA). It also suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.