Molecular mechanism of asthma and its novel molecular target therapeutic agent

Suraya, Ratoe; Nagano, Tatsuya; Katsurada, Masahiro; Sekiya, Reina; Kobayashi, Kazuyuki; Nishimura, Yoshihiro

doi:10.1016/j.resinv.2020.12.007

Cited by 13 publications

(12 citation statements)

References 80 publications

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“…A prominent example is an anti-IgE antibody (Omalizumab) [80], which inhibits the binding of IgE to mast cells and eosinophils and furthermore reduces the production of IgE by B cells [153]. In addition, several other antibodies targeting the IL-4 and IL-5 pathways have been investigated [154].…”

Section: Therapeutic Approaches Tackling Asthma and Pulmonary Fibrosismentioning

confidence: 99%

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Hetzel

Ackermann

Lachmann

2021

IJMS

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Macrophages act as immune scavengers and are important cell types in the homeostasis of various tissues. Given the multiple roles of macrophages, these cells can also be found as tissue resident macrophages tightly integrated into a variety of tissues in which they fulfill crucial and organ-specific functions. The lung harbors at least two macrophage populations: interstitial and alveolar macrophages, which occupy different niches and functions. In this review, we provide the latest insights into the multiple roles of alveolar macrophages while unraveling the distinct factors which can influence the ontogeny and function of these cells. Furthermore, we will highlight pulmonary diseases, which are associated with dysfunctional macrophages, concentrating on congenital diseases as well as pulmonary infections and impairment of immunological pathways. Moreover, we will provide an overview about different treatment approaches targeting macrophage dysfunction. Improved knowledge of the role of macrophages in the onset of pulmonary diseases may provide the basis for new pharmacological and/or cell-based immunotherapies and will extend our understanding to other macrophage-related disorders.

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Section: Therapeutic Approaches Tackling Asthma and Pulmonary Fibrosismentioning

confidence: 99%

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Hetzel

Ackermann

Lachmann

2021

IJMS

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“…AMG282 is currently under investigation in a phase 2b study, whose primary endpoint is the impact of drug treatment on AAER [ 16 ]. At present ongoing trials also focus on astegolimab, a monoclonal antibody targeting the ST2 receptor of IL-33 [ 4 ]. In this regard, the phase 2b randomized, double-blind, dose-ranging, placebo-controlled study ZENYATTA has recently shown that astegolimab was able to significantly decrease AAER in patients with severe asthma [ 107 ].…”

Section: Anti-alarminsmentioning

confidence: 99%

“…Asthma is a chronic inflammatory disease of the respiratory tract, usually characterized by variable airflow limitation and affecting more than 300 million people worldwide [ 1 , 2 ]. Asthma phenotypes are heterogeneous and include eosinophilic patterns, underpinned by either allergic or non-allergic mechanisms, as well as neutrophilic and paucigranulocytic traits [ 3 , 4 , 5 ]. Eosinophilic asthma is driven by complex cellular and molecular pathways which shape the so-called type 2 (T2-high) airway inflammation, a term based on the key pathogenic roles played by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2), releasing the interleukins 4 (IL-4), 5 (IL-5), 9 (IL-9), and 13 (IL-13) [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma

Pelaia

Longhini

et al. 2021

Biomedicines

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Alarmins are innate cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), which are mainly produced by airway epithelium and exert a prominent role in asthma pathobiology. In particular, several environmental factors such as allergens, cigarette smoking, airborne pollutants, and infectious agents trigger the release of alarmins, which in turn act as upstream activators of pro-inflammatory pathways underlying type 2 (T2-high) asthma. Indeed, alarmins directly activate group 2 innate lymphoid cells (ILC2), eosinophils, basophils, and mast cells and also stimulate dendritic cells to drive the commitment of naïve T helper (Th) cells towards the Th2 immunophenotype. Therefore, TSLP, IL-33, and IL-25 represent suitable targets for add-on therapies of severe asthma. Within this context, the fully human anti-TSLP monoclonal antibody tezepelumab has been evaluated in very promising randomized clinical trials. Tezepelumab and other anti-alarmins are thus likely to become, in the near future, valuable therapeutic options for the biological treatment of uncontrolled severe asthma.

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“…Asthma is a chronic obstructive respiratory disease, mainly characterized by airflow limitation due to bronchial inflammation and airway remodeling [ 1 , 2 ]. A hallmark of asthma is the heterogeneity of airway inflammation, expressed by several phenotypes sustained by underlying different endotypes, which consist of complex cellular and molecular pathogenic mechanisms ( Figure 1 ) [ 3 , 4 , 5 ]. The most frequent endotypes are grouped under the umbrella term “type 2” (T2) asthma, which includes allergic and non-allergic traits, mostly outlined by eosinophilic inflammation [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma

Pelaia

Crimi

et al. 2021

IJMS

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Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

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Molecular mechanism of asthma and its novel molecular target therapeutic agent

Cited by 13 publications

References 80 publications

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma

Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma

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