A role for B cells in organic dust induced lung inflammation

Respiratory Research

Research

William W. West¹  Kristi J. Warren²  Amy J. Nelson²  Jill A. Poole²  Debra J. Romberger³  Todd A. Wyatt⁴  Michael J. Duryee⁵  Ted R. Mikuls⁵  Geoffrey M. Thiele⁵ 

[1] Pathology and Microbiology Department, UNMC, Omaha, NE, USA;Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center (UNMC), 985990 Nebraska Medical Center, 68198-5990, Omaha, NE, USA;Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service, Omaha, NE, USA;Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center (UNMC), 985990 Nebraska Medical Center, 68198-5990, Omaha, NE, USA;Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service, Omaha, NE, USA;Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center (UNMC), 985990 Nebraska Medical Center, 68198-5990, Omaha, NE, USA;Department of Environmental, Agricultural, and Occupational Health, UNMC, Omaha, NE, USA;Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service, Omaha, NE, USA;Rheumatology Division, Department of Internal Medicine, UNMC, Omaha, NE, USA;

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

DOI  :  10.1186/s12931-017-0703-x

 received in 2017-09-15, accepted in 2017-12-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAgriculture 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.MethodsUsing 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.ResultsODE-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.ConclusionsLung 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】

CC BY   
© The Author(s). 2018