A role for B cells in organic dust induced lung inflammation

Respiratory Research

William W. West¹  Todd A. Wyatt²  Kristi J. Warren²  Jill A. Poole²  Amy J. Nelson²  Debra J. Romberger²  Michael J. Duryee³  Geoffrey M. Thiele³  Ted R. Mikuls³ 

[1] Pathology and Microbiology Department, UNMC;Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center (UNMC);Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service;

关键词: Lung;    Inflammation;    Autoantibody;    Immunoglobulin;    Organic dust;    MAA adduct;   

DOI  :  10.1186/s12931-017-0703-x

来源: DOAJ

【 摘 要 】

Abstract Background Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity. Methods Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected. Results ODE-induced neutrophil influx in lavage fluid was not reduced in BCR KO animals, but there was reduction in TNF-α, IL-6, CXCL1, and CXCL2 release. ODE-induced lymphoid aggregates failed to develop in BCR KO mice. There was a decrease in ODE-induced lung tissue CD11c+CD11b+ exudative macrophages and compensatory increase in CD8+ T cells in lavage fluid of BCR KO animals. Compared to saline, there was an expansion of conventional B2-, innate B1 (CD19+CD11b+CD5+/−)-, and memory (CD19+CD273+/-CD73+/−) B cells following ODE exposure in WT mice. Autoreactive responses including serum IgG anti-citrullinated protein antibody (ACPA) and anti-malondialdehyde-acetaldehyde (MAA) autoantibodies were increased in ODE treated WT mice as compared to saline control. B cells and serum immunoglobulins were not detected in BCR KO animals. Conclusions Lung tissue staining for citrullinated and MAA modified proteins were increased in ODE-treated WT animals, but not BCR KO mice. These studies show that agriculture organic dust induced lung inflammation is dependent upon B cells, and dust exposure induces an autoreactive response.

【 授权许可】

Unknown