Chronic eosinophilic pneumonia (CEP) is a rare eosinophilic lung disease. We report a 61-year-old man with asthma who presented with progressive exertional dyspnoea for 2 months and worsening productive cough for 2 weeks. Peripheral blood eosinophilia was 15% (1314 cells/μL), and chest computed tomography showed bilateral peripheral, upper-lobe-predominant opacities. Bronchoalveolar lavage (BAL) revealed marked neutrophil predominance (85%) with only 6% eosinophils. Empirical antibiotics produced no clinical or radiographic improvement. Because clinical and radiological suspicion for CEP remained high despite discordant BAL findings, surgical lung biopsy was performed, demonstrating prominent eosinophilic infiltration with an organizing pneumonia pattern, supporting a diagnosis of CEP. The patient responded well to systemic corticosteroids. This case highlights the role of surgical lung biopsy in suspected CEP with atypical BAL findings and illustrates that organizing pneumonia may occur within the histopathological spectrum of CEP.

RNA sequencing (RNA-seq) analysis revealed transcriptional features indicative of sustained immunosuppression within regulatory T cells (Tregs) isolated from atherosclerotic tissues, highlighting the critical contribution of immune checkpoint (ICP) receptor-ligand interactions to atherosclerosis progression. To comprehensively characterize the roles of ICP signaling in this context, we integrated transcriptomic profiling, quantitative RT-PCR, and flow cytometry analysis, yielding several key findings: (1) Multiomics integration revealed global transcriptomic alterations in ICP receptors and ligands across diverse tissues, immune cell types, and disease stages in both human and murine models of atherosclerosis; (2) Several ICP components demonstrated functional relevance, including dual-function ligand CD155 (PVR); inhibitory ligands Lgals3 and Itgb1; stimulatory ligands Tnfrsf9 and CD48; and inhibitory receptors Havcr2 and Lair1. These molecules act as microenvironmental sensors, dynamically responding to atherosclerotic cues; (3) Experimental validation confirmed upregulation of the CD155-TIGIT axis within immune cells of atherosclerotic plaques. Notably, CD155 expression positively correlated with CD206 expression in both CD11b+CD11c+ and CD11b-CD11c+ cells, irrespective of tissue context; and (4) The CD206+ macrophages/DCs-CD155-TIGIT+ Treg axis emerged as a potential ICP-mediated pathway that confers immunoregulatory protection against atherosclerosis progression. Collectively, these findings uncover novel immunomodulatory roles for ICP ligands in atherosclerosis, expanding their known functions beyond adaptive immune regulation to include modulation of innate immune responses within atherosclerotic lesions.

Fibroblast migration contributes to the spatial organization of tissue repair and extracellular matrix remodeling, but the transcriptional mechanisms regulating this process under physiologically relevant mechanical conditions remain incompletely understood. We investigated whether GATA4 regulates fibroblast migration in a tissue-of-origin-dependent manner. Cardiac fibroblasts (CFs), lung fibroblasts (LFs), and tail-tip fibroblasts (TTFs) were isolated from neonatal male and female Gata4fl/fl mice and cultured on 8-kPa polydimethylsiloxane substrates. CF behavior on 8-kPa substrates was first compared with that on conventional tissue-culture plastic. Gata4 was subsequently deleted by adenoviral Cre transduction, and multiple features of steady-state migration were quantified by live-cell imaging. CFs cultured on 8-kPa substrates exhibited a smaller cell area and greater migration speed, displacement, and directional persistence than cells cultured on plastic, establishing a physiologically relevant mechanical baseline. Baseline Gata4 expression was highest in CFs, intermediate in LFs, and lowest in TTFs, whereas adenoviral Cre reduced Gata4 expression by more than 90% in all three populations. Gata4 deletion produced distinct migratory responses according to fibroblast source. In CFs, Gata4 loss reduced instantaneous speed, line speed, segment length, and directional persistence while increasing cell area. LFs showed modest increases in instantaneous speed, path speed, normalized 1-h path distance, and segment length without a clear change in directional persistence, whereas TTF migration was comparatively insensitive to Gata4 loss. Integrated effect-size analysis confirmed that the coordinated alteration of migration rate and directionality was most pronounced in CFs. RNA-seq analysis of adult CFs further showed enrichment of general motility and actin-remodeling programs following Gata4 deletion, without coordinated enrichment of lamellipodium and focal-adhesion programs. Together, these findings indicate that GATA4 supports efficient and persistent fibroblast migration in a fibroblast-source-dependent manner under physiologically relevant mechanical conditions.

Metastatic recurrence is still a major problem for triple-negative breast cancer (TNBC). Neutrophil extracellular traps (NETs) in the pulmonary microenvironment are known to play key roles in the metastatic colonization and outgrowth of TNBC. However, the exact role that NETs play in determining the phenotypic plasticity and reactivation of disseminated tumor cells (DTCs) during acute relapse remains unclear. Here, we utilized an orthotopic, acute recurrent metastasis mouse model by transplanting 4T1 cells into wild-type or NET-deficient (Padi4-/- ) mice, followed by primary tumor resection. Although Padi4 deficiency had no effect on the growth of the primary tumors, it significantly reduced lung metastasis and prolonged survival. 4T1 cells re-established from WT lungs displayed a highly proliferative epithelial phenotype, whereas those from Padi4-/- mice appeared to maintain a quiescent mesenchymal state. Crucially, tissue-adapted NET-forming pulmonary neutrophils could facilitate a mesenchymal-to-epithelial transition (MET)-like switch by robustly upregulating transforming growth factor-beta (TGF-β) negative regulators, thereby attenuating autocrine signaling. Collectively, our findings suggest that tissue-adapted NETs serve as crucial microenvironmental cues that support the exit from quiescence and drive metastatic outgrowth, highlighting a promising perioperative therapeutic target for TNBC.