Allergy (and clinical immunology)

An overactive population of natural killer cells in children with eczema may worsen skin damage and provoke allergic sensitivity or development of asthma.

"A blog about allergy, asthma & immunology"

Asthma is a heterogeneous, chronic respiratory disease affecting 300 million people and is thought to be driven by different inflammatory endotypes influenced by a myriad of genetic and environmental factors. The complexity of asthma has rendered it challenging to develop preventative and disease modifying therapies and it remains an unmet clinical need. Whilst many factors have been implicated in asthma pathogenesis and exacerbations, evidence indicates a prominent role for respiratory viruses. However, advances in culture-independent detection methods and extensive microbial profiling of the lung, have also demonstrated a role for respiratory bacteria in asthma. In particular, airway colonization by the Proteobacteria species Nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) is associated with increased risk of developing recurrent wheeze and asthma in early life, poor clinical outcomes in established adult asthma and the development of more severe inflammatory phenotypes. Furthermore, emerging evidence indicates that bacterial-viral interactions may influence exacerbation risk and disease severity, highlighting the need to consider the impact chronic airway colonization by respiratory bacteria has on influencing host responses to viral infection. In this review, we first outline the currently understood role of viral and bacterial infections in precipitating asthma exacerbations and discuss the underappreciated potential impact o

The exposure of the airway epithelium to external stimuli such as allergens, microbes, and air pollution triggers the release of the alarmin cytokines IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). IL-25, IL-33 and TSLP interact with their ligands, IL-17RA, IL1RL1 and TSLPR respectively, expressed by hematopoietic and non-hematopoietic cells including dendritic cells, ILC2 cells, endothelial cells, and fibroblasts. Alarmins play key roles in driving type 2-high, and to a lesser extent type 2-low responses, in asthma. In addition, studies in which each of these three alarmins were targeted in allergen-challenged mice showed decreased chronicity of type-2 driven disease. Consequently, ascertaining the mechanism of activity of these upstream mediators has implications for understanding the outcome of targeted therapies designed to counteract their activity and alleviate downstream type 2-high and low effector responses. Furthermore, identifying the factors which shift the balance between the elicitation of type 2-high, eosinophilic asthma and type-2 low, neutrophilic-positive/negative asthma by alarmins is essential. In support of these efforts, observations from the NAVIGATOR trial imply that targeting TSLP in patients with tezepelumab results in reduced asthma exacerbations, improved lung function and control of the disease. In this review, we will discuss the mechanisms surrounding the secretion of IL-25, IL-33, and TSLP from the airway epithelium and how thi

Severe bronchiolitis (i.e., bronchiolitis or first episode of wheeze requiring hospitalization) during infancy is a heterogeneous condition associated with an increased risk for childhood asthma development (1,2). Bronchiolitis cohort studies have identified early-life environmental, genetic and immune risk factors for childhood asthma development by carrying out analysis at single level (e.g., associations with respiratory virus types, host immune response or the microbiome composition of the host) (3,4). However, severe bronchiolitis pathogenesis involves interaction of factors at multiple levels (e.g., genome, epigenome, transcriptome, metabolome, microbiome). Optimistically, the increasing use of omics methodologies in observational studies allows for a more holistic approach, that can shed light on severe bronchiolitis pathophysiology by identifying distinct biological processes associated with long-term sequelae like asthma (5). In addition, mechanistic studies are required to validate and test identified pathogenetic pathways from omics studies.To further address the issues outlined above, our Research Topic congregates evidence from observational and interventional studies exploring the severe bronchiolitis to childhood asthma causal pathway with the aim to identify severe bronchiolitis endotypes that can guide predictive (i.e., response to treatment) and prognostic (i.e., association with long-term respiratory sequelae) enrichment strategies (see Figure 1). Th

Asthma is a heterogeneous respiratory disease characterized by airflow obstruction, bronchial hyperresponsiveness and airway inflammation. Approximately 10% of asthma patients suffer from uncontrolled severe asthma (SA). A major difference between patients with SA from those with mild-to-moderate asthma is the resistance to common glucocorticoid treatments. Thus, steroid-unresponsive uncontrolled asthma is a hallmark of SA. An impediment in the development of new therapies for SA is a limited understanding of the range of immune responses and molecular networks that can contribute to the disease process. Typically SA is thought to be characterized by a Th2-low and Th17-high immunophenotype, accompanied by neutrophilic airway inflammation. However, Th2-mediated eosinophilic inflammation, as well as mixed Th1/Th17-mediated inflammation, is also described in SA. Thus, existing studies indicate that the immunophenotype of SA is diverse. This review attempts to summarize the interplay of different immune mediators and related mechanisms that are associated with airway inflammation and the immunobiology of SA.