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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Authors: Nishima S, Miyanaga A, Saito S, Yuasa M, Takahashi S, Kashiwada T, Sugano T, Noro R, Minegishi Y, Terasaki Y, Saito Y, Kubota K, Seike M, Gemma A Abstract Osimertinib is the standard treatment for epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer. However, drug-induced interstitial lung disease (ILD) is recognized as a serious adverse event associated with EGFR-tyrosine kinase inhibitors (TKIs). We herein report a 78-year-old woman with stage IV lung adenocarcinoma harboring an EGFR L858R mutation on exon 21 who received rechallenge treatment with afatinib after osimertinib-induced ...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
ConclusionsWe are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSIONS: We demonstrated a significant reduction in Cdyn in subjects with ILD using photoplethysmography. This non-invasive method might be a novel, promising tool for evaluating fibrosis progression in ILD. PMID: 32999175 [PubMed - as supplied by publisher]
Source: Journal of Nippon Medical School - Category: Universities & Medical Training Authors: Tags: J Nippon Med Sch Source Type: research
Conclusions: The overall incidence of fatal toxic effects related to EGFR-TKIs was 1.33%, and the major fatal cause was ILD, followed by pneumonia, respiratory failure and diarrhea. The susceptible factor of fatal toxic effects related to EGFR-TKIs was the Japanese group. This study provided a capability for clinicians to predict and detect high-risk populations of fatal toxic effects. PMID: 32944317 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
Authors: Troung L, Pourzand L, Volkmann ER Abstract Infection with the coronavirus disease 2019 (Covid-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), manifests in a myriad of ways ranging from asymptomatic disease to pneumonia and acute respiratory distress syndrome. Advanced age and underlying cardiovascular/pulmonary conditions appear to increase the risk for Covid-19 complications [1,2]. PMID: 32934125 [PubMed - as supplied by publisher]
Source: Journal of Rheumatology - Category: Rheumatology Tags: J Rheumatol Source Type: research
Authors: Santhanam S, Mohanasundaram K, Krishnan S Abstract Interstitial lung disease (ILD) is an umbrella term for lung disease characterised by inflammation and fibrosis of the interstitium. ILD can be idiopathic or secondary to connective tissue disorders, drugs or environmental exposures. Before labelling it as idiopathic we have to rule out secondary causes. ILD is one of the most common extra-articular manifestations of connective tissue diseases (CTDs), causing significant morbidity and mortality. Patients with pre-existing CTD can develop ILD; some patients develop ILD against the background of either one o...
Source: Journal of the Royal College of Physicians of Edinburgh - Category: General Medicine Tags: J R Coll Physicians Edinb Source Type: research
AbstractPurposeIdiopathic Pulmonary Fibrosis is a progressive and fatal interstitial lung disease (ILD) characterized by a typical radiographic or histologic usual interstitial pneumonia (UIP) pattern.  In 2018, diagnostic categories of UIP based on computed tomography patterns were revised by the Fleischner Society. The study aimed to describe differences in comorbidities and spirometry in ILD patients that were characterized by high-resolution computed tomography (HRCT) images as having a typic al, probable, indeterminate, and alternative diagnosis of UIP.MethodsWe retrospectively studied 80 ILD patients from 2017 t...
Source: Lung - Category: Respiratory Medicine Source Type: research
ConclusionHRCT findings in ASS-associated ILD are often non-specific; nevertheless, it is important to consider this diagnosis, especially in patients presenting with acute onset of symptoms.
Source: Japanese Journal of Radiology - Category: Radiology Source Type: research
Up to 15% of patients with chronic interstitial lung disease (cILD) will remain clinically unclassifiable (i.e. unclassifiable ILD, uILD) despite thorough clinical evaluation and multidisciplinary team discussion (MDT) [1, 2]. This diagnostic uncertainty translates into uncertainty in expected prognosis and initial treatment approach (e.g. immunosuppression versus anti-fibrotic medications) for patients with uILD, and it often precludes enrolment into clinical trials. Peripheral blood telomere length (TL) is a genomic biomarker that has been associated with prognosis and harm from immunosuppression in IPF [3, 4]. TL has re...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Original Articles: Research letters Source Type: research
CONCLUSION: CT detects everolimus-induced pneumonitis at a subclinical stage. In this setting, CT findings, clinical severity, and PFT do not clearly correlate. Opacification pattern analysis seems to be of importance when assessing the severity of CT findings. Asymptomatic patients with positive CT findings should be closely monitored to timely initiate specific treatment. PMID: 32819165 [PubMed - as supplied by publisher]
Source: Acta Radiologica - Category: Radiology Authors: Tags: Acta Radiol Source Type: research
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