CX3CR1-fractalkine axis drives kinetic changes of monocytes in fibrotic interstitial lung diseases

In this study, we analysed circulating and lung resident monocyte populations, and assessed their phenotype and recruitment from the blood to the lung in ILD. Flow cytometry analysis of blood samples for quantifying circulating monocytes was performed in 105 subjects: 83 with ILD (n=36, n=28 and n=19 for nonspecific interstitial pneumonia, hypersensitivity pneumonitis and connective-tissue disease-associated ILD, respectively), as well as 22 controls. Monocyte localisation and abundance were assessed using immunofluorescence and flow cytometry of lung tissue. Monocyte populations were cultured either alone or with endothelial cells to assess fractalkine-dependent transmigration pattern. We show that circulating classical monocytes (CM) were increased in ILD compared with controls, while nonclassical monocytes (NCM) were decreased. CM abundance correlated inversely with lung function, while NCM abundance correlated positively. Both CCL2 and CX3CL1 concentrations were increased in plasma and lungs of ILD patients. Fractalkine co-localised with ciliated bronchial epithelial cells, thereby creating a chemoattractant gradient towards the lung. Fractalkine enhanced endothelial transmigration of NCM in ILD samples only. Immunofluorescence, as well as flow cytometry, showed an increased presence of NCM in fibrotic niches in ILD lungs. Moreover, NCM in the ILD lungs expressed increased CX3CR1, M2-like and phagocytic markers. Taken together, our data support that in ILD, fractalkine dr...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung biology and experimental studies, Interstitial and orphan lung disease Original Articles: Interstitial lung disease and basic science Source Type: research

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In conclusion, IIP patients with a probable UIP pattern on initial chest CT had a better prognosis and longer time to first AE than those with a UIP pattern. However, when baseline data and longitudinal behaviour provided a final diagnosis of IPF, CT pattern was not associated with these outcomes. This suggests diagnostic heterogeneity among patients with a probable UIP pattern.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research
Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity. We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independe...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research
CONCLUSIONS.—: In a specially constructed multidisciplinary discussion exercise, it was found that peribronchiolar metaplasia affecting more than half the bronchioles or more than 2 foci of peribronchiolar metaplasia per square centimeter of biopsy area was strongly associated with a confident diagnosis of fibrotic hypersensitivity pneumonitis. Giant cells or granulomas were only found in cases with a greater than 50% diagnostic confidence in hypersensitivity pneumonitis. Conversely, greater numbers of fibroblast foci per square centimeter and increasing measured amounts of subpleural fibrosis favored a diagnosis of ...
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD. We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression analysis using Nanostr...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Interstitial and orphan lung disease, Mechanisms of lung disease Original Articles: Interstitial lung disease and basic sceince Source Type: research
Conclusion IPF, CHP, and CTD-ILD were the main differential diagnoses in patients with HRCT patterns of typical, probable and indeterminate UIP. Patients with HRCT typical UIP pattern were m ore likely to die or had lung transplantation in the follow-up.
Source: Jornal Brasileiro de Pneumologia - Category: Respiratory Medicine Source Type: research
ConclusionsThis study demonstrated that patients who developed GGO exhibited worse outcomes among non ‐small‐cell lung cancer patients receiving anti‐PD‐1 therapies.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSIONS The carrier status of MUC5B variants was an indicator of reduced prognosis and increased exacerbations of RA-ILD. PMID: 32142504 [PubMed - as supplied by publisher]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
ConclusionAnti-EJ syndrome was found to be a relatively common ASS subtype, with a favorable outcome. A notable proportion of the patients experienced RP-ILD, which was prone to OP on HRCT and a higher CAR, and needed aggressive management.Key Points• ILD was the most common initial manifestation of anti-glycyl tRNA synthetase syndrome.• RP-ILD was notable in anti-EJ positive patients.• Anti-EJ positive patients possessed a favorable long-term prognosis, but easily relapsed.
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Rationale: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. Patient concerns: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritabil...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Interstitial lung disease (ILD) is a frequent complication of patients with connective tissue disease (CTD) and significantly affects morbidity and mortality. Disease course may vary from stable or mildly progressive to more severe, with rapid loss of lung function. We conducted a search of PubMed (National Library of Medicine) and the Web of Science Core Collection using the key words lung, pulmonary, pneumonia, pneumonitis, and alveolar and subtypes of CTD. All clinical studies from January 1, 1980, through September 1, 2018, were reviewed for descriptions of specific therapies and their efficacy or safety and were categ...
Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Review Source Type: research
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