BPIFA1 Regulates Interferon-Mediated Lung Neutrophil Recruitment During Acute Inflammation

BPIFA1 (BPI-fold containing group A member 1) is an airway host-protective protein with immunomodulatory properties that binds to LPS and is regulated by infectious and inflammatory signals. Differential expression of BPIFA1 has been widely reported in lung disease, yet the biological significance of this observation is unclear. We sought to understand the role of BPIFA1 fluctuations in modulating lung inflammation. We treated WT and bpifa1-/- mice with intranasal LPS and performed transcriptomic analyses to determine the immune effects of BPIFA1 deficiency. Transcriptomic analysis revealed a signature of 379 genes that differentiated bpifa1-/- mice from WT. During acute lung inflammation, the most strongly downregulated innate immunity genes in bpifa1-/- mice were cxcl9 and cxcl10. This was consistent with significantly decreased expression of IFN-g, IFN-l and downstream IFN-stimulated genes (ISG) and IFN-regulatory factors (IRF) important for innate immune responses. BPIFA1-/- and WT controls were treated with 5 micrograms of intranasal LPS and gene expression analysis was performed at 0, 8, and 24 hours. Controls received intranasal PBS. Groups: WT at 0 hours (n=6), bpifa1-/- at 0 hours (n=6), WT at 8 hours (n=6), bpifa1-/- at 0 hours (n=5), WT at 24 hours (n=5), bpifa1-/- at 0 hours (n=5)