Background Transforming growth factor (TGF)-β1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-β1 production and thus a potential regulator of airway remodeling. Objectives To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. Methods The airways of Shp2flox/flox mice were infected with recombinant adenovirus vectors expressing a Cre recombinase–green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-β1. Results Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-β1 production by these cells correlated with the extent of shp2 gene expression. Conclusions SHP2 activities in airway epithelial cells appear to modulate TGF-β1 production and, in turn, regulate allergic airway remodeling following allergen provocation. Clinical Implications Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung dysfunction associated with allergen challenge. As such, SHP2 represents a potentially novel therapeutic target for the treatment of asthmatics.
These data demonstrate that ILN serves as a 'weapon' pool of Th1 cells following BCG vaccination, and these cells are ready for the migration into the inflamed lungs upon the allergen challenge, thereby inhibiting allergen-induced airway disorder.
Dear editor, In 2013, we have reported chest tightness being the only respiratory symptom among 24 asthmatic patients on presentation, 1 and referred to this type of asthma as chest tightness variant asthma (CTVA). Compared with patients with classic asthma (CA) or cough variant asthma (CVA), 2,3 patients with CTVA also presented with eosinophilic airway inflammation. However, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear. We therefore sought to explore the therapeutic response to standard asthma treatments among 76 patients with CTVA in a 52-week multicenter, prospective, real-world study. The study was conducted in 16 centers (see Supporting Information) in mainland China. Participants were recruited between April 1, 2015 and March 31, 2018 (Figure 1). We recruited treatment-naive patients (14-80 years of age) who had a history of chest tightness for at least 6 months. The definition of CTVA was made based on the chest tightness being the sole symptom and at least one of the following conditions was met: (a) an increase of >12% and >200 mL in forced expiratory volume in 1 s (FEV 1) after inhaling salbutamol; (b) airway hyperresponsiveness as evidenced by a positive finding of bronchial provocation test; (c) a weekly variability in diurnal peak expiratory flow (PEF) of greater than 10%; and (d) a marked clinical improvement in response to β2 receptor agonists, with or without inhaled corticosteroids (ICS). All patients were treated with ICS plus long-acting β2 receptor agonist based on the Global Initiative for Asthma (GINA) guidelines. The following baseline characteristics were collected from eligible patients: age, gender, the history of atopy, smoking status, body mass index (BMI), FEV 1 (percent predicted), the ratio of FEV 1 /forced vital capacity (FVC), diurnal variation in PEF, the fraction of exhaled nitric oxide (FeNO), patient-rated anxiety scale (SAS) This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Objective. Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first identified in December 2019 in Wuhan, China, and has since spread globally, resulting in an ongoing pandemic. However, the study of asymptomatic patients is still rare, and the understanding of its potential transmission risk is still insufficient. In this study, epidemiological investigations were conducted in the Zhejiang province to understand the epidemiology and clinical characteristics of asymptomatic patients with COVID-19. Methods. This retrospective study was carried out on 22 asymptomatic patients and 234 symptomatic patients with COVID-19 who were hospitalized in Zhejiang Duodi Hospital from January 21 to March 16, 2020. The characteristics of epidemiology, demography, clinical manifestations, and laboratory data of mild patients were compared and analyzed. Results. The median age was 28 years in asymptomatic patients and 48 years in symptomatic patients. The proportion who were female was 77.3% in asymptomatic patients and 36.3% in symptomatic patients (p<0.001). The proportion of patients with coexisting diseases was 4.5% in asymptomatic patients and 38.0% in symptomatic patients (p=0.002). The proportion of patients with increased CRP was 13.6% in the asymptomatic group and 61.1% in the symptomatic group (p<0.001). The proportion of patients received antiviral therapy was 45.5% in the asymptomatic group and 97.9% in the symptomatic group (p<0.001). The proportion of patients received oxygen therapy was 22.7% in the asymptomatic group and 99.1% in symptomatic patients (p<0.001). By March 16, 2020, all patients were discharged from the hospital, and no symptoms had appeared in the asymptomatic patients during hospitalization. The median course of infection to discharge was 21.5 days in asymptomatic patients and 22 days in symptomatic patients. Conclusions. Asymptomatic patients are also infectious; relying only on clinical symptoms, blood cell tests, and radiology examination will lead to misdiagnosis of most patients, leading to the spread of the virus. Investigation of medical history is the best strategy for screening asymptomatic patients, especially young people, women, and people without coexisting disease, who are more likely to be asymptomatic when infected. Although the prognosis is good, isolation is critical for asymptomatic patients, and it is important not to end isolation early before a nucleic acid test turns negative.
The NOD-like receptor protein 3 (NLRP3) inflammasome is a protein complex that regulates innate immune responses by activating caspase-1 and the inflammatory cytokines interleukin (IL)-1β and IL-18. Multiple studies have demonstrated the importance of the NLRP3 inflammasome in the development of immune and inflammation-related diseases, including arthritis, Alzheimer’s disease, inflammatory bowel disease, and other autoimmune and autoinflammatory diseases. This review first explains the activation and regulatory mechanism of the NLRP3 inflammasome. Secondly, we focus on the role of the NLRP3 inflammasome in various inflammation-related diseases. Finally, we look forward to new methods for targeting the NLRP3 inflammasome to treat inflammation-related diseases, and provide new ideas for clinical treatment.
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