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

被引：24

作者：

Morissette, Mathieu C. ^{[1
,15
]}

Gao, Yang ^{[1
,2
,3
,16
]}

Shen, Pamela ^{[4
]}

Thayaparan, Danya ^{[4
]}

Berube, Jean-Christophe ^{[5
]}

Pare, Peter D. ^{[6
,7
]}

Brandsma, Corry-Anke ^{[8
,9
]}

Hao, Ke ^{[10
,11
]}

Bosse, Yohan ^{[5
,12
]}

Ettinger, Rachel ^{[13
]}

Herbst, Ronald ^{[13
]}

Humbles, Alison A. ^{[13
]}

Kolbeck, Roland ^{[13
]}

Zhong, Nanshan ^{[2
,3
]}

Chen, Rongchang ^{[2
,3
]}

Stampfli, Martin R. ^{[1
,14
]}

机构：

[1] McMaster Univ, McMaster Immunol Res Ctr, Dept Pathol & Mol Med, Hamilton, ON, Canada

[2] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China

[4] McMaster Univ, Med Sci Grad Program, Hamilton, ON, Canada

[5] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada

[6] Univ British Columbia, St Pauls Hosp, Dept Med, Vancouver, BC, Canada

[7] Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada

[8] Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[10] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA

[11] Tongji Univ, Shanghai Peoples Hosp 10, Dept Resp Med, Shanghai, Peoples R China

[12] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada

[13] MedImmune LLC, Gaithersburg, MD USA

[14] McMaster Univ, St Josephs Healthcare, Firestone Inst Resp Hlth, Dept Med, Hamilton, ON, Canada

[15] Univ Laval, Fac Med, CRIUCPQ, Quebec City, PQ, Canada

[16] Capital Med Univ, Beijing Anzhen Hosp, Dept Pulm & Crit Care, Beijing, Peoples R China

来源：

PHYSIOLOGICAL REPORTS | 2016年 / 4卷 / 24期

基金：

加拿大健康研究院; 中国国家自然科学基金;

关键词：

Animal model; autoantibodies; BAFF; cigarette smoke; COPD;

D O I：

10.14814/phy2.13057

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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 4days of cigarette smoke exposure and remained elevated following 8 and 24weeks 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.

引用

页数：11

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