The basic immunology of asthma

Hammad, Hamida; Lambrecht, Bart

doi:10.1016/j.cell.2021.02.016

Cited by 436 publications

(345 citation statements)

References 149 publications

(173 reference statements)

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“…Asthma is a complex and heterogenous disease [ 51 ]. Clinical and experimental data demonstrate that eosinophils contribute to the airway hyperreactivity seen in asthmatic individuals that have allergic airway disease [ 8 , 10 , 11 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production

et al. 2021

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Exposure to the mold, Aspergillus, is ubiquitous and generally has no adverse consequences in immunocompetent persons. However, invasive and allergic aspergillosis can develop in immunocompromised and atopic individuals, respectively. Previously, we demonstrated that mouse lung eosinophils produce IL-17 in response to stimulation by live conidia and antigens of A. fumigatus. Here, we utilized murine models of allergic and acute pulmonary aspergillosis to determine the association of IL-23, IL-23R and RORɣt with eosinophil IL-17 expression. Following A. fumigatus stimulation, a population of lung eosinophils expressed RORɣt, the master transcription factor for IL-17 regulation. Eosinophil RORɣt expression was demonstrated by flow cytometry, confocal microscopy, western blotting and an mCherry reporter mouse. Both nuclear and cytoplasmic localization of RORɣt in eosinophils were observed, although the former predominated. A population of lung eosinophils also expressed IL-23R. While expression of IL-23R was positively correlated with expression of RORɣt, expression of RORɣt and IL-17 was similar when comparing lung eosinophils from A. fumigatus-challenged wild-type and IL23p19-/- mice. Thus, in allergic and acute models of pulmonary aspergillosis, lung eosinophils express IL-17, RORɣt and IL-23R. However, IL-23 is dispensable for production of IL-17 and RORɣt.

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Section: Discussionmentioning

confidence: 99%

Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production

et al. 2021

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“…In addition, patients with severe asthma may present with persistent eosinophilic inflammation in the absence of specific IgE [ 27 , 28 ]. Phenotypic heterogeneity of asthma and the variable treatment responses to Th2-directed trials and therapies have brought out the speculation of non-Th2 inflammation in the pathogenesis of allergic airway inflammation; the categorization of asthma based on distinct mechanistic pathways was proposed as an algorithm to tailor treatment strategies [ 29 , 30 , 31 , 32 ]. With the intention to leverage laboratory evidence for precision asthma treatment, two major asthma endotypes have been described ( Table 1 ).…”

Section: Asthma Endotypesmentioning

confidence: 99%

“…Biomarkers for Th2-low asthma have not been widely investigated. Neutrophils, matrix metallopeptidase 9 (MMP-9) and IL-6 have all been proposed as potential candidates, but none have been shown to represent all phenotypic subgroups of the Th2-low asthma endotype [ 29 , 32 ]. Application of multi-omics approaches encompassing transcriptomics, epigenomics, metagenomics, metabolomics, and proteomics, in combination with clinical features and laboratory data will enable asthma endotyping to be more informative and allow the designation of precision treatment strategies [ 44 , 45 ].…”

Section: Asthma Endotypesmentioning

confidence: 99%

Asthma in the Precision Medicine Era: Biologics and Probiotics

Chiu

Huang

2021

IJMS

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Asthma is a major global health issue. Over 300 million people worldwide suffer from this chronic inflammatory airway disease. Typical clinical symptoms of asthma are characterized by a recurrent wheezy cough, chest tightness, and shortness of breath. The main goals of asthma management are to alleviate asthma symptoms, reduce the risk of asthma exacerbations, and minimize long-term medicinal adverse effects. However, currently available type 2 T helper cells (Th2)-directed treatments are often ineffective due to the heterogeneity of the asthma subgroups, which manifests clinically with variable and poor treatment responses. Personalized precision therapy of asthma according to individualized clinical characteristics (phenotype) and laboratory biomarkers (endotype) is the future prospect. This mini review discusses the molecular mechanisms underlying asthma pathogenesis, including the hot sought-after topic of microbiota, add-on therapies and the potential application of probiotics in the management of asthma.

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“…As a result, complex and tightly regulated immunological networks evolved to provide both effective tolerance to environmental antigens and protection against potentially invasive airborne pathogenic threats. Many different cell types, such as epithelial cells, myeloid cells and innate and adaptive lymphocytes contribute to cellular and humoral immunity in the lung ( 2 ). While the lung already harbors numerous immune cells in the steady-state, their frequencies and relative proportions strongly change during infections, tissue damage or chronic inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

2021

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During the last decade, group-2 innate lymphoid cells (ILC2s) have been discovered and successfully established as crucial mediators of lung allergy, airway inflammation and fibrosis, thus affecting the pathogenesis and clinical course of many respiratory diseases, like for instance asthma, cystic fibrosis and chronic rhinosinusitis. As an important regulatory component in this context, the local pulmonary milieu at inflammatory tissue sites does not only determine the activation status of lung-infiltrating ILC2s, but also influences their motility and migratory behavior. In general, many data collected in recent murine and human studies argued against the former concept of a very strict tissue residency of innate lymphoid cells (ILCs) and instead pointed to a context-dependent homing capacity of peripheral blood ILC precursors and the inflammation-dependent capacity of specific ILC subsets for interorgan trafficking. In this review article, we provide a comprehensive overview of the so far described molecular mechanisms underlying the pulmonary migration of ILC2s and thereby the numeric regulation of local ILC2 pools at inflamed or fibrotic pulmonary tissue sites and discuss their potential to serve as innovative therapeutic targets in the treatment of inflammatory lung diseases.

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The basic immunology of asthma

Cited by 436 publications

References 149 publications

Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production

Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production

Asthma in the Precision Medicine Era: Biologics and Probiotics

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

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