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Bronchiolitis obliterans (BO) is a chronic airway disease that was often indicated by the pathological presentation of narrowed and irreversible airways. However, the molecular mechanisms of BO pathogenesis remain unknown. Although neutrophil extracellular traps (NETs) can contribute to inflammatory disorders, their involvement in BO is unclear. This study aims to identify potential signaling pathways in BO by exploring the correlations between NETs and BO. GSE52761 and GSE137169 datasets were downloaded from gene expression omnibus (GEO) database. A series of bioinformatics analyses such as differential expression analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were performed on GSE52761 and GSE137169 datasets to identify BO potential signaling pathways. Two different types of BO mouse models were constructed to verify NETs involvements in BO. Additional experiments and bioinformatics analysis using human small airway epithelial cells (SAECs) were also performed to further elucidate differential genes enrichment with their respective signaling pathways in BO. Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes. Besides, we found that neutrophil extracellular traps (NETs) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further confirmed NETs activation in BO, where neutrophil elastase (NE) and myeloperoxidase (MPO) expression were found significantly elevated. Transcriptomic and bioinformatics analysis of NETs treated-SAECs also revealed that NETs-DEGs were primarily associated through inflammatory and epithelial-to-mesenchymal transition (EMT) -related pathways. Our study provides novel clues towards the understanding of BO pathogenesis, in which NETs contribute to BO pathogenesis through the activation of inflammatory and EMT associated pathways. The completion of our study will provide the basis for potential novel therapeutic targets in BO treatment., (© 2023. The Author(s).)

Background: Analyzed the clinical features and treatment process of the patient suffering from immunodeficiency with systemic lupus erythematosus(SLE)-like syndrome in a novel mutation of PRKDC., Case Presentation: The patient had multiple positive auto-antibodies, chest CT and bronchoscopy showed Diffuse alveolar hemorrhage(DAH), and psychiatric symptoms showed brain atrophy by magnetic resonance imaging (MRI). Whole exon sequencing showed that novel complex heterozygous mutations of PRKDC gene (C. 1777 - 710_1777-709INSA (IVS16/IC16), C.1337T > A(p.Phe446Tyr). The mature B cell (CD19 + CD27 + CD38 dimIgD IgM-) were absent. The treatment of high-dose methylprednisolone (MP) and cyclophosphamide(CTX) can quickly relieve the symptoms of the patient., Conclusion: We described the case of an infant immunodeficiency with SLE like-syndrome, which may cause by PRKDC mutation, treated successfully with high-dose MP and CTX., (© 2023. BioMed Central Ltd., part of Springer Nature.)