Open AccessRole of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice
Author(s) -
Morissette Mathieu C.,
Gao Yang,
Shen Pamela,
Thayaparan Danya,
Bérubé JeanChristophe,
Paré Peter D.,
Brandsma CorryAnke,
Hao Ke,
Bossé Yohan,
Ettinger Rachel,
Herbst Ronald,
Humbles Alison A.,
Kolbeck Roland,
Zhong Nanshan,
Chen Rongchang,
Stämpfli Martin R.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13057
Subject(s) - autoantibody , medicine , cigarette smoke , immunology , b cell activating factor , antibody , environmental health , b cell
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 ( TLT s) 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 TLT s 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 ( TLT s) 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.