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CD8+T Cells Medite Lung Pathology в отсутствие PD-L1 и I типа Интерферон сигнализации после заражения LCMV.

CD8+T клетки имеют решающее значение для адаптивной иммунной реакции на вирусные патогены. Однако подавляющее воздействие антигена может привести к их истощению, характеризующемуся снижением функции воздействия, неспособностью очистить вирус и повышением регулирования ингибиционных рецепторов, включая запрограммированную клеточную смерть 1 (PD-1). Однако изнурённые ответы T-клеток могут быть "переоборудованы" путем ограничения PD-1 или первичного лиганда PD-1: PD-L1. Кроме того, отсутствие интерферонального рецептора I I IFNAR1 также приводит к истощению клеток Т и к стойкости вируса в мышах,

Совпадение в аннотации оригинала
CD8+ T cells are critical to the adaptive immune response against viral pathogens. However, overwhelming antigen exposure can result in thei … and instead, it converted chronic LCMV-Arm infection into a lethal disease characterized by severe lung inflammation with an infiltration of neutrophils and T cells. Depletion of CD8+ T cells, but not neutrophils, rescued mice from lethal disease, demonstrating that IFNAR1 is required to prevent T cell exhaustion and virus persistence in LCMV-Arm infe …

Outcomes of Lung Transplantation for Sarcoidosis in the Lung Allocation Score Era.

PURPOSE: Sarcoidosis is an uncommon indication for lung transplantation, and survival for these recipients has not been fully characterized. We investigated outcomes after lung transplantation for sarcoidosis in comparison to more common indications. METHODS: United Network for Organ Sharing data were retrospectively reviewed for lung transplant candidates and recipients listed for sarcoidosis, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis (IPF) between 2005 and 2023. Survival and perioperative outcomes were compared among groups. RESULTS: Of the 20,411 lung …

Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.

The vast majority of cancer-related deaths are attributed to metastasis. The lung, being a common site for cancer metastasis, is highly prone to being a target for multiple cancer types and causes a heavy disease burden. Accumulating evidence has demonstrated that tumor metastasis necessitates continuous interactions between tumor cells and distant metastatic niches. Nevertheless, a comprehensive elucidation of the underlying mechanisms governing lung-specific metastasis still poses a formidable challenge. In this review, we depict the lung susceptibility and the molecular profiles of tumors w…

Single lung transplantation is safe when the other lung is declined†.

OBJECTIVES: Single lung transplant (SLT) is an acceptable treatment modality for certain patients with end-stage lung disease. SLT occurs when two appropriate donor lungs are split between recipients ('split singles') or when one donor lung is adequate for transplant and the other lung is declined ('isolated single'). There is a paucity of literature investigating the outcomes in patients who received an isolated SLT. This study analyses the characteristics and survival outcomes of isolated SLT recipients. METHODS: The transplant database at our institution was queried for all lung transplant…

An alveolus lung-on-a-chip model of Mycobacterium fortuitum lung infection.

Lung disease due to non-tuberculous mycobacteria (NTM) is rising in incidence. While both two dimensional cell culture and animal models exist for NTM infections, a major knowledge gap is the early responses of human alveolar and innate immune cells to NTM within the human alveolar microenvironment. Here we describe development of a humanized, three-dimensional, alveolus lung-on-a-chip (ALoC) model of Mycobacterium fortuitum lung infection that incorporates only primary human cells such as pulmonary vascular endothelial cells in a vascular channel, and type I and II alveolar cells and monocyte…

An alveolus lung-on-a-chip model of Mycobacterium fortuitum lung infection.

Lung disease due to non-tuberculous mycobacteria (NTM) is rising in incidence. Although both two-dimensional cell culture and animal models exist for NTM infections, a major knowledge gap is the early responses of human alveolar and innate immune cells to NTM within the human alveolar microenvironment. Here, we describe the development of a humanized, three-dimensional, alveolus lung-on-a-chip (ALoC) model of Mycobacterium fortuitum lung infection that incorporates only primary human cells, such as pulmonary vascular endothelial cells, in a vascular channel, and type I and II alveolar cells an…

The gut microbiome in end-stage lung disease and lung transplantation.

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant rec…

The National Lung Matrix Trial of personalized therapy in lung cancer.

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke1-3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcom…

Transbronchial lung biopsy for the diagnosis of IgG4-related lung disease.

AIMS: The diagnosis of IgG4-related disease (IgG4-RD) requires a multidisciplinary approach, in which histology plays an important role. Although a diagnosis was previously established by the use of surgically resected specimens, there is increasing clinical demand to diagnose this systemic condition by the use of biopsies. The aim of the present study was to elucidate how useful transbronchial lung biopsies (TBLBs) are for this diagnostic purpose. METHODS AND RESULTS: The study cohort consisted of 20 consecutive patients diagnosed with IgG4-RD in other organs who underwent TBLB for potential…

Meta-markers for the differential diagnosis of lung cancer and lung disease.

UNLABELLED: Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical informa…

[Surgical lung biopsy for the management of diffuse interstitial lung disease].

OBJECTIVE: To evaluate the role of surgical lung biopsy (SLB) in the management of diffuse interstitial lung disease (DILD) with no specific diagnosis. METHODS: We conducted a retrospective analysis of 179 cases with DILD of non-specific diagnosis after non-invasive methods and minimally invasive processes, including bronchoscopy and CT-guided lung biopsy, were performed SLB at Peking Union Medical College Hospital between 2006 and 2012. Patient demographics, surgical approach, number and site of biopsies, post-operative complications and postoperative pathological diagnosis and treatment wer…

Lung transplantation in adults and children: putting lung function into perspective.

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. …

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS…

Lung deposition and pharmacokinetics of nebulized cyclosporine in lung transplant patients.

BACKGROUND: Inhaled cyclosporine (CsA) is being investigated as a prophylaxis for lung transplant rejection. Lung deposition and systemic exposure of nebulized CsA in lung transplant patients was evaluated as part of the Phase 3 cyclosporine inhalation solution (CIS) trial (CYCLIST). METHODS: Ten patients received 300 mg of CIS (62.5 mg/mL CsA in propylene glycol) admixed with 148 MBq of Tc-DTPA (technetium-99m bound to diethylenetriaminepentaacetic acid) administered using a Sidestream(®) disposable jet nebulizer. Deposition was assessed using a dual-headed gamma camera. Blood samples were c…

Hydatid disease of the lung presenting with hemoptysis and simulating a lung abscess.

Hydatidosis is one of the most important zoonotic diseases in the world. In this report, we describe a 25-year-old patient from Guntur district of Andhra Pradesh who presented with cough, chest pain, dyspnoea, and hemoptysis due to hydatid disease of the lung. Although it is one of the less common causes of hemoptysis, hydatid disease of the lung requires greater attention in countries such as India, where hydatid cyst disease is common.

Imaging of sarcoidosis of the airways and lung parenchyma and correlation with lung function.

Imaging has a prominent role in the assessment of sarcoidosis diagnosis and outcome, which are extremely variable. Chest radiography staging helps predict the probability of spontaneous remission, and stage IV is associated with higher mortality. However, the reproducibility of reading is poor and changes in radiography and lung function are inconsistently correlated, which may be problematic for the monitoring of disease and treatment response. Chest computed tomography (CT) makes a great diagnostic contribution in difficult cases. Bilateral hilar lymphadenopathy with peri-lymphatic micronodu…

Altered lung motion is a sensitive indicator of regional lung disease.

Since lung diseases adversely affect airflow during breathing, they must also alter normal lung motion, which can be exploited to detect these diseases. However, standard imaging techniques such as CT and MRI imaging during breath-holds provide little or no information on lung motion and cannot detect diseases that cause subtle changes in lung structure. Phase-contrast X-ray imaging provides images of high contrast and spatial resolution with temporal resolutions that allow multiple images to be acquired throughout the respiratory cycle. Using X-ray phase-contrast imaging, coupled with velocim…

One-lung ventilation and HIF1alpha expression in lung cancer and pneumothorax.

BACKGROUND/AIM: A prospective study was designed to investigate the effects of anesthesia, particularly that of the one-lung ventilation procedure (OLV), on the expression of hypoxia-inducible factor 1alpha (HIF1alpha) in patients with lung carcinomas and pneumothorax. MATERIALS AND METHODS: The immunohistochemical expression of HIF1alpha was studied in formalin-fixed paraffin-embedded tissues from 60 patients who had undergone thoracic surgery for lung cancer (n=48) or pneumothorax (n=12) under OLV general anesthesia. RESULTS: There was a significant, and rather unexpected, association of H…