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      Biology and Function of Eosinophils in Chronic Rhinosinusitis With or Without Nasal Polyps

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          Abstract

          Chronic rhinosinusitis (CRS) with or without nasal polyposis is a complex medical condition characterized by varying patterns of chronic innate and adaptive mucosal inflammation. Treatment of CRS has been traditionally limited to corticosteroids and sinus surgery; however, novel biologics have more recently been evaluated as steroid- and surgery-sparing options. While it is clear that there are different subtypes or endotypes of CRS, perhaps the most frequent presentation involves the features of type 2 inflammation, including a prominent tissue eosinophilia component. The purpose of this review is to provide an update on eosinophil biology as well as on the potential contribution of eosinophils and their mediators to the pathophysiology of CRS, drawing mechanistic conclusions mainly from studies of human sinus mucosal tissues, nasal secretions, and benefits (or lack thereof) from the use of various pharmacotherapies. The unavoidable conclusion derived from this approach is that eosinophils themselves cannot fully explain the underlying pathophysiology of this complex disorder.

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          Most cited references75

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          Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma

          Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
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            Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

            Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.
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              Eosinophils: changing perspectives in health and disease

              Key Points Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have provided a more sophisticated understanding of eosinophil effector functions and a more nuanced view of their contributions to the pathogenesis of various diseases, including asthma and respiratory allergies, eosinophilic gastrointestinal diseases, hypereosinophilic syndromes and parasitic infection. Eosinophils are granulocytes that develop in the bone marrow from pluripotent progenitors in response to cytokines, such as interleukin-5 (IL-5), IL-3 and granulocyte–macrophage colony-stimulating factor (GM-CSF). Mature eosinophils are released into the peripheral blood and enter tissues in response to cooperative signalling between IL-5 and eotaxin family chemokines. Eosinophils in peripheral blood and tissues are uniquely identified by their bilobed nuclei, their large specific granules that store cytokines, cationic proteins and enzymes, and their expression of the IL-5 receptor and CC-chemokine receptor 3 (CCR3). In addition, the receptors sialic acid-binding immunoglobulin-like lectin 8 (SIGLEC-8) and SIGLEC-F are expressed by human and mouse eosinophils, respectively. IL-5 has a central and profound role in all aspects of eosinophil development, activation and survival. IL-5 is produced by T helper 2 (TH2) cells, and more recently the contributions of the epithelium-derived innate cytokines thymic stromal lymphopoietin (TSLP), IL-25 and IL-33 in promoting eosinophilia via the induction of IL-5 have also been recognized. Although eosinophil responses are influenced by cytokines produced by T cells, eosinophils in turn modulate the functions of B and T cells. Eosinophils also communicate with a range of innate immune cells (such as mast cells, dendritic cells, macrophages and neutrophils). Eosinophils serve to bridge innate and adaptive immunity by regulating the production of chemoattractants and cytokines (including CC-chemokine ligand 17 (CCL17), CCL22, a proliferation-inducing ligand (APRIL) and IL-6) and via antigen presentation. Both successful and unsuccessful attempts to target eosinophils have yielded remarkable insights into their contribution to disease pathogenesis. Many eosinophil-associated inflammatory conditions have been shown to be heterogeneous in nature. As such, successful therapeutic strategies will depend on the correlation of disease activity with dysregulated eosinophil function as well as the identification of the crucial molecules that regulate eosinophil accumulation in the affected tissues. Supplementary information The online version of this article (doi:10.1038/nri3341) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Allergy Asthma Immunol Res
                Allergy Asthma Immunol Res
                AAIR
                Allergy, Asthma & Immunology Research
                The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
                2092-7355
                2092-7363
                January 2021
                09 June 2020
                : 13
                : 1
                : 8-22
                Affiliations
                Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
                Author notes
                Correspondence to Bruce S. Bochner, MD. Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 E. Huron Street, Room M-306, Chicago, IL 60611, USA. Tel: +1-312-695-4000; Fax: +1-312-695-4141; bruce.bochner@ 123456northwestern.edu
                Author information
                https://orcid.org/0000-0002-9411-6009
                https://orcid.org/0000-0002-2608-6610
                Article
                10.4168/aair.2021.13.1.8
                7680832
                33191674
                84ee173c-2ebd-40a5-9931-dfe23aabfb58
                Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 April 2020
                : 23 April 2020
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases, CrossRef https://doi.org/10.13039/100000060;
                Award ID: U19 AI136443
                Award ID: K23 AI141694
                Award ID: P01 AI145818
                Categories
                Review

                Immunology
                eosinophils,nasal polyps,sinusitis,biologics,inflammation
                Immunology
                eosinophils, nasal polyps, sinusitis, biologics, inflammation

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