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Nature Communications Dec 2023Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the...
Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1Rag2 mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1Rag2 mice as a mouse model for fibrosis research.
Topics: Animals; Mice; Pulmonary Fibrosis; Immunity, Innate; Interleukin-33; Lymphocytes; Fibrosis; Collagen; Lung; Mice, Inbred C57BL; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38097562
DOI: 10.1038/s41467-023-43336-6 -
European Respiratory Review : An... Sep 2023Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis... (Review)
Review
Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis (SAPF), which may become progressive. Genetic profiles differ between patients with progressive and self-limiting disease. The mechanisms of fibrosis in SAPF are not fully understood, but SAPF is likely a distinct clinicopathological entity, rather than a continuum of acute inflammatory sarcoidosis. Risk factors for the development of SAPF have been identified; however, at present, it is not possible to make a robust prediction of risk for an individual patient. The bulk of fibrotic abnormalities in SAPF are located in the upper and middle zones of the lungs. A greater extent of SAPF on imaging is associated with a worse prognosis. Patients with SAPF are typically treated with corticosteroids, second-line agents such as methotrexate or azathioprine, or third-line agents such as tumour necrosis factor inhibitors. The antifibrotic drug nintedanib is an approved treatment for slowing the decline in lung function in patients with progressive fibrosing interstitial lung diseases, but more evidence is needed to assess its efficacy in SAPF. The management of patients with SAPF should include the identification and treatment of complications such as bronchiectasis and pulmonary hypertension. Further research is needed into the mechanisms underlying SAPF and biomarkers that predict its clinical course.
Topics: Humans; Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Sarcoidosis; Risk Factors; Disease Progression
PubMed: 37758275
DOI: 10.1183/16000617.0085-2023 -
Respirology (Carlton, Vic.) Mar 2022
Topics: Alveolitis, Extrinsic Allergic; Humans; Pulmonary Fibrosis
PubMed: 35146840
DOI: 10.1111/resp.14225 -
QJM : Monthly Journal of the... Nov 2021
Topics: COVID-19; Humans; Lung; Pulmonary Fibrosis; SARS-CoV-2
PubMed: 34002238
DOI: 10.1093/qjmed/hcab121 -
Archivos de Bronconeumologia Apr 2022
Topics: COVID-19; Humans; Lung; Pulmonary Fibrosis; Tomography, X-Ray Computed
PubMed: 35491285
DOI: 10.1016/j.arbres.2022.03.007 -
Frontiers in Immunology 2023Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The... (Review)
Review
Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.
Topics: Humans; Extracellular Traps; COVID-19; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Pulmonary Fibrosis; Inflammation
PubMed: 37828990
DOI: 10.3389/fimmu.2023.1254310 -
Translational Research : the Journal of... Jul 2019Pulmonary fibrosis refers to the development of diffuse parenchymal abnormalities in the lung that cause dyspnea, cough, hypoxemia, and impair gas exchange, ultimately... (Review)
Review
Pulmonary fibrosis refers to the development of diffuse parenchymal abnormalities in the lung that cause dyspnea, cough, hypoxemia, and impair gas exchange, ultimately leading to respiratory failure. Though pulmonary fibrosis can be caused by a variety of underlying etiologies, ranging from genetic defects to autoimmune diseases to environmental exposures, once fibrosis develops it is irreversible and most often progressive, such that fibrosis of the lung is one of the leading indications for lung transplantation. This review aims to provide a concise summary of the recent advances in our understanding of the genetics and genomics of pulmonary fibrosis, idiopathic pulmonary fibrosis in particular, and how these recent discoveries may be changing the clinical approach to diagnosing and treating patients with fibrotic interstitial lung disease.
Topics: Early Diagnosis; Genetic Predisposition to Disease; Humans; Idiopathic Pulmonary Fibrosis; Phenotype; Telomere; Translational Research, Biomedical
PubMed: 30768925
DOI: 10.1016/j.trsl.2019.02.001 -
American Journal of Respiratory Cell... Aug 2023Lungs are constantly exposed to environmental perturbations and therefore have remarkable capacity to regenerate in response to injury. Sustained lung injuries, aging,... (Review)
Review
Lungs are constantly exposed to environmental perturbations and therefore have remarkable capacity to regenerate in response to injury. Sustained lung injuries, aging, and increased genomic instability, however, make lungs particularly susceptible to disrepair and fibrosis. Pulmonary fibrosis constitutes a major cause of morbidity and is often relentlessly progressive, leading to death from respiratory failure. The pulmonary vasculature, which is critical for gas exchanges and plays a key role during lung development, repair, and regeneration, becomes aberrantly remodeled in patients with progressive pulmonary fibrosis. Although capillary rarefaction and increased vascular permeability are recognized as distinctive features of fibrotic lungs, the role of vasculature dysfunction in the pathogenesis of pulmonary fibrosis has only recently emerged as an important contributor to the progression of this disease. This review summarizes current findings related to lung vascular repair and regeneration and provides recent insights into the vascular abnormalities associated with the development of persistent lung fibrosis.
Topics: Humans; Pulmonary Fibrosis; Lung; Fibrosis; Lung Injury; Respiratory Insufficiency; Idiopathic Pulmonary Fibrosis
PubMed: 37126595
DOI: 10.1165/rcmb.2022-0431TR -
Pediatrics and Neonatology Mar 2022Supplemental oxygen is often used to treat newborns with respiratory disorders. Exposure to high concentration of oxygen and long-term oxygen causes inflammation and... (Review)
Review
Supplemental oxygen is often used to treat newborns with respiratory disorders. Exposure to high concentration of oxygen and long-term oxygen causes inflammation and acute lung injury. The acute inflammatory phase is followed by a fibroproliferative repair phase, leading to lung fibrosis. Many infants with lung fibrosis develop significant respiratory morbidities including reactive airways dysfunction and obstructive lung disease during childhood. Despite the absence of effective treatments and the incomplete understanding regarding mechanisms underlying fibrosis, extensive literature regarding lung fibrosis from in vitro and in vivo hyperoxia-exposed models is available. In this review, we discuss molecular mediators and signaling pathways responsible for increased fibroblast proliferation and collagen production, excessive extracellular matrix accumulation, and eventually, lung fibrosis. We discuss each of these mediators separately to facilitate clear understanding as well as significant interactions occurring among these molecular mediators and signaling pathways.
Topics: Humans; Hyperoxia; Infant, Newborn; Inflammation; Lung; Oxygen; Pulmonary Fibrosis
PubMed: 35181258
DOI: 10.1016/j.pedneo.2021.11.008 -
Respirology (Carlton, Vic.) Sep 2022
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial
PubMed: 35764391
DOI: 10.1111/resp.14320