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Войти в исследования Journal of inflammation research · 2026
Iron Dyshomeostasis and Divergent Antigen Presentation Remodeling in Bronchiectasis: A Dual-Dataset Transcriptomic Analysis.
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Dang Yuhai, Li Xiaojuan, Li Zhitong, Zhou Yue, Luo Jin, Wang Ke, Kong Jinliang
Аннотация
BACKGROUND: Bronchiectasis features persistent neutrophilic inflammation with recurrent infections, yet why abundant immune infiltrates fail to clear bacteria remains unclear. Ferroptosis-iron-dependent regulated cell death-modulates immunity in oncology but is unexplored in chronic airway diseases.
METHODS: We performed dual-dataset transcriptomic analysis integrating bulk lung RNA-sequencing (GSE153131: bronchiectasis, normal, pneumonia) and an in vitro BEAS-2B epithelial microarray dataset (1,004 differentially expressed genes at FDR < 0.05). Ferroptosis gene-set scoring, immune deconvolution, orthogonal neutrophil validation, and Gene Set Enrichment Analysis were conducted. Bulk tissue analysis (Dataset 1) was based on a single bronchiectasis sample and interpreted descriptively.
RESULTS: Bulk tissue showed iron dyshomeostasis (HMOX1↑, FTL↓, TFRC↑) with myeloid chemokine hyperactivation (CXCL9↑ 5.9-fold, CXCL10↑ 2.4-fold) and T-cell effector attenuation (CD3D↓ 46%, GZMB↓ 54%). PTGS2 was unchanged. In the epithelial model, ferroptosis suppressor genes were coordinately downregulated (25/39), and MHC class II machinery was significantly suppressed (CIITA↓: logFC=-0.90, P=0.022; HLA-DMA↓: logFC=-1.11, P=0.010; HLA-DMB↓: logFC=-1.12, P=0.036), while MHC class I (B2M↑) was preserved. T-cell markers were absent from epithelium, confirming interstitial origin of T-cell attenuation.
CONCLUSION: Bronchiectasis exhibits compartment-specific iron-immune dysregulation: epithelial iron dyshomeostasis with selective MHC-II downregulation coexisting with myeloid chemokine hyperactivation. This "recruitment-presentation uncoupling" may explain the inflammation-clearance paradox. Iron-dependent dioxygenases (TET/PHD/JMJD) are proposed as intermediaries linking iron to CIITA regulation.
METHODS: We performed dual-dataset transcriptomic analysis integrating bulk lung RNA-sequencing (GSE153131: bronchiectasis, normal, pneumonia) and an in vitro BEAS-2B epithelial microarray dataset (1,004 differentially expressed genes at FDR < 0.05). Ferroptosis gene-set scoring, immune deconvolution, orthogonal neutrophil validation, and Gene Set Enrichment Analysis were conducted. Bulk tissue analysis (Dataset 1) was based on a single bronchiectasis sample and interpreted descriptively.
RESULTS: Bulk tissue showed iron dyshomeostasis (HMOX1↑, FTL↓, TFRC↑) with myeloid chemokine hyperactivation (CXCL9↑ 5.9-fold, CXCL10↑ 2.4-fold) and T-cell effector attenuation (CD3D↓ 46%, GZMB↓ 54%). PTGS2 was unchanged. In the epithelial model, ferroptosis suppressor genes were coordinately downregulated (25/39), and MHC class II machinery was significantly suppressed (CIITA↓: logFC=-0.90, P=0.022; HLA-DMA↓: logFC=-1.11, P=0.010; HLA-DMB↓: logFC=-1.12, P=0.036), while MHC class I (B2M↑) was preserved. T-cell markers were absent from epithelium, confirming interstitial origin of T-cell attenuation.
CONCLUSION: Bronchiectasis exhibits compartment-specific iron-immune dysregulation: epithelial iron dyshomeostasis with selective MHC-II downregulation coexisting with myeloid chemokine hyperactivation. This "recruitment-presentation uncoupling" may explain the inflammation-clearance paradox. Iron-dependent dioxygenases (TET/PHD/JMJD) are proposed as intermediaries linking iron to CIITA regulation.