Addressing unmet needs in understanding asthma mechanisms

Edwards, Michael R.; Saglani, Sejal; Schwarze, Jürgen; Skevaki, Chrysanthi; Smith, Jaclyn A.; Ainsworth, Ben; Almond, M.; Andreakos, Evangelos; Belvisi, Maria G.; Chung, Kian Fan; Cookson, William; Cullinan, Paul; Hawrylowicz, Catherine M.; Lommatzsch, Marek; Jackson, David J.; Lutter, René; Marsland, Benjamin J.; Moffatt, Miriam F.; Thomas, Mike; Virchow, J. Christian; Xanthou, Georgina; Edwards, Jessica; Walker, Samantha; Johnston, Sebastian L.

doi:10.1183/13993003.02448-2016

Cited by 50 publications

(29 citation statements)

References 475 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prevalence of allergic asthma has dramatically increased worldwide during the last decade. Asthma is a chronic inflammatory disease of the airways associated with airway hyper-responsiveness to inhaled allergens and deregulation of type 2 immunity (36); however, its pathogenesis is still not fully understood. Asthma is characterized by an expansion of CD4 + helper T lymphocytes (Th2, Th17), increased production of the Th2 cytokines IL-4, IL-5, and IL-13, an increased level of allergen-specific immunoglobulin E (IgE), eosinophilia and inflammation of the airways (37).…”

Section: Discussionmentioning

confidence: 99%

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

et al. 2018

View full text Add to dashboard Cite

CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9+ IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9+ B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9+ B cells in human and mouse. The profile of CD9+ B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9+ B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19+CD9+ B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9+ B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9+ B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9+ B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Obstructive pulmonary diseases have been widely studied, with over 300 million people worldwide affected by both asthma and Chronic Obstructive Pulmonary Disease (COPD) [1,2,3,4,5,6]. Given their increasing burden and financial impact [7,8,9], more attention is rising for the late-onset asthma phenotype [10], that differs from early-onset asthma with respect to genetic susceptibility, environmental exposures, pathogenic mechanisms, comorbidities, prognosis and treatment response [10,11,12,13,14]. Evidence is emerging that, besides tobacco smoking, risk factors, such as respiratory infections, poor nutritional status, chronic asthma, impaired lung growth, poor socio-economic status and genetic factors are also important for COPD development [1].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Asthma and COPD and Blood Eosinophil Count in a Middle-Aged Belgian Population

Wijnant

Lahousse

Buyzere

et al. 2019

JCM

View full text Add to dashboard Cite

Various phenotypes exist in asthma and Chronic Obstructive Pulmonary Disease (COPD). These are important to identify in order to guide treatment decisions. We aim to investigate the prevalence and clinical characteristics of obstructive airway diseases in the middle-aged population. We estimated the prevalence of COPD and/or asthma in the Asklepios cohort study (Belgium), using information from the third European Community Respiratory Health Survey (ECRHS3), medical records, and spirometry. Respiratory symptoms, respiratory medication, and current disease status distinguished clinical from sub-clinical cases. In addition, we compared the blood eosinophil count/µL (median [IQR]) between cases and controls. Of the 2221 participants (mean age 56.1 ± 5.9 years; 48.7% males), 138 (6.2%) participants had clinical current asthma, 22 (1.0%) participants had sub-clinical ever asthma, 102 (4.6%) had sub-clinical spirometry-defined COPD, 104 (4.6%) participants had clinical spirometry-confirmed COPD, and 11 (0.5%) had asthma and COPD overlap (ACO). Clinical current asthma (160.0 [110.0–250.0]), sub-clinical ever asthma (170.0 [110.0–230.0]), and clinical COPD (160.0 [110.0–220.0])—but less sub-clinical COPD (140.0 [90.0–210.0])—had higher eosinophil counts, compared to controls (130.0 [80.0–200.0]). We conclude that obstructive airway diseases are prevalent in the middle-aged Asklepios cohort. Moreover, the systemic eosinophil count is increased in clinical COPD cases, and in asthma cases regardless of clinical remission.

show abstract

“…It is now well established that there are multiple phenotypes and endotypes of asthma [ 1 , 2 ]. 15 to 20 years ago it was widely believed that asthma was an allergic/atopic disease caused by allergen exposure.…”

Section: Introductionmentioning

confidence: 99%

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration

et al. 2018

View full text Add to dashboard Cite

The World Asthma Phenotypes (WASP) study started in 2016 and has been conducted in five centres, in the UK, New Zealand, Brazil, Ecuador and Uganda.The objectives of this study are to combine detailed biomarker and clinical information in order to 1) better understand and characterise asthma phenotypes in high-income countries (HICs) and low and middle-income countries (LMICs), and in high and low prevalence centres; 2) compare phenotype characteristics, including clinical severity; 3) assess the risk factors for each phenotype; and 4) assess how the distribution of phenotypes differs between high prevalence and low prevalence centres.Here we present the rationale and protocol for the WASP study to enable other centres around the world to carry out similar analyses using a standardised protocol. Large collaborative and integrative studies like this are essential to further our understanding of asthma phenotypes. The findings of this study will help elucidate the aetiological mechanisms of asthma and might potentially identify new causes and guide the development of new treatments, thereby enabling better management and prevention of asthma in both HICs and LMICs.

show abstract

Addressing unmet needs in understanding asthma mechanisms

Cited by 50 publications

References 475 publications

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

Prevalence of Asthma and COPD and Blood Eosinophil Count in a Middle-Aged Belgian Population

Understanding asthma phenotypes: the World Asthma Phenotypes (WASP) international collaboration

Contact Info

Product

Resources

About