B-Cell Activating Factor Secreted by Neutrophils Is a Critical Player in Lung Inflammation to Cigarette Smoke Exposure

Abstract

Cigarette smoke (CS) is the major cause of chronic lung injuries, such as chronic obstructive pulmonary disease (COPD). In patients with severe COPD, tertiary lymphoid follicles containing B lymphocytes and B cell-activating factor (BAFF) overexpression are associated with disease severity. In addition, BAFF promotes adaptive immunity in smokers and mice chronically exposed to CS. However, the role of BAFF in the early phase of innate immunity has never been investigated. We acutely exposed C57BL/6J mice to CS and show early BAFF expression in the bronchoalveolar space and lung tissue that correlates to airway neutrophil and macrophage influx. Immunostaining analysis revealed that neutrophils are the major source of BAFF. We confirmed in vitro that neutrophils secrete BAFF in response to cigarette smoke extract (CSE) stimulation. Antibody-mediated neutrophil depletion significantly dampens lung inflammation to CS exposure but only partially decreases BAFF expression in lung tissue and bronchoalveolar space suggesting additional sources of BAFF. Importantly, BAFF deficient mice displayed decreased airway neutrophil recruiting chemokines and neutrophil influx while the addition of exogenous BAFF significantly enhanced this CS-induced neutrophilic inflammation. This demonstrates that BAFF is a key proinflammatory cytokine and that innate immune cells in particular neutrophils, are an unconsidered source of BAFF in early stages of CS-induced innate immunity.

BAFF Blockade Attenuates DSS-Induced Chronic Colitis via Inhibiting NLRP3 Inflammasome and NF-κB Activation

“…Research related to autoimmune hepatitis (AIH) has shown that serum BAFF levels are significantly higher in patients with AIH, compared to hepatitis patients and healthy controls, with positive correlations to AST, ALT, TBIL, and soluble CD30, implying BAFF contributes to liver injury in patients with AIH ( 26 ). BAFF expression was significantly higher in small pulmonary artery endothelial cells, alveolar epithelial cells, and alveolar macrophages in COPD patients, while circulating BAFF concentrations were higher in patients who smoked compared to non-smokers, suggesting that BAFF was associated with impaired lung function, hypoxia severity in COPD patients ( 27 – 29 ). We previously found elevated BAFF in serum, stool and colon tissue of adults with ulcerative colitis and Crohn’s disease, and serum BAFF levels correlated with disease activity, ESR, TNF-α, and IL-1β in ulcerative colitis patients ( 8 ).…”

Neutrophils in chronic inflammatory diseases

“…In vitro, BAFF secretion was increased in neutrophils treated with cigarette smoke extract. Accordingly, the depletion of neutrophils reduces BAFF expression in the lung, and mice that are deficient in BAFF have decreased neutrophil infiltration in the lung [ 24 ]. Rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factors and anti-citrullinated protein antibodies (ACPAs) in human serum [ 25 ].…”

Increased B Cell-Activating Factor Expression Is Associated with Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps

“…Exaggerated or dysregulated B cell function can drive T2 mucosal inflammatory states in nasal mucosa via local antibody production and other inflammatory cell recruitment [32]. BAFF is expressed on several immune and nonimmune cells and acts as a crucial biomolecule in sustaining B cell homeostasis [16,33]. Previous studies found that BAFF overexpressed peripheral blood and local tissues in tumor, inflammatory, and autoimmune diseases, and soluble form of BAFF was demonstrated to be a promising biomarker in reflecting disease activity and predicting prognosis [14,17,21,33].…”