The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs. The progression and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13. Although CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68- and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with LPS. We found that TNF-α and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-κB and JAK/STAT pathways, respectively. We also found that blood TNF-α and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF-α contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-κB and JAK/STAT pathways are required to induce the expression of this major chemokine.
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http://dx.doi.org/10.4049/jimmunol.1900790 | DOI Listing |
Eur J Med Res
January 2025
Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis, nomogram model for its prognosis and acute exacerbation was constructed.
Methods: Two hundred and sixty eight patients with IPF were grouped with different severity according to fibrosis area, serum Club cell secretory protein 16(CC16) was compared between these groups. All patients were randomly divided into training and testing sets.
Sci Rep
January 2025
Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Automated tools for quantification of idiopathic pulmonary fibrosis (IPF) can aid in ensuring reproducibility, however their complexity and costs can differ substantially. In this retrospective study, two automated tools were compared in 45 patients with biopsy proven (12/45) and imaging-based (33/45) IPF diagnosis (mean age 74 ± 9 years, 37 male) for quantification of pulmonary fibrosis in CT. First, a tool that identifies multiple characteristic lung texture features was applied to measure multi-texture fibrotic lung (MTFL) by combining the amount of ground glass, reticulation, and honeycombing.
View Article and Find Full Text PDFEur Respir J
January 2025
Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Rationale: Although a relationship between the Gas6/AXL pathway and pulmonary fibrosis (PF) has been suggested, the precise mechanisms and clinical implications of the AXL pathway in idiopathic pulmonary fibrosis (IPF) are still unclear.
Methods: Constitutive and conditional AXL-knockout mice were generated and injected with bleomycin (BLM) to induce pulmonary fibrosis. The expression of AXL and macrophage subtypes in BLM-injected mice and patients with IPF was analysed using flow cytometry.
FASEB J
January 2025
Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Obstructive sleep apnea (OSA) is increasingly recognized for its link to idiopathic pulmonary fibrosis (IPF), though the underlying mechanisms remain poorly understood. Histone lysine demethylase 6B (KDM6B) may either prevent or promote organ fibrosis, but its specific role in IPF is yet to be clarified. This study aimed to investigate the function and mechanisms of KDM6B in IPF and the exacerbating effects of OSA.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
The Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
Pulmonary fibrosis is a pathological manifestation that occurs upon lung injury and subsequence aberrant repair with poor prognosis. However, current treatment is limited and does not distinguish different disease stages. Here, we aimed to study the differential functions of Axl, a receptor tyrosine kinase expressing on both macrophages and fibroblasts, in the whole course of pulmonary fibrosis.
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