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Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma

Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5–10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strate...

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Autores principales: Salter, Brittany M., Ju, Xiaotian, Sehmi, Roma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920418/
https://www.ncbi.nlm.nih.gov/pubmed/33669458
http://dx.doi.org/10.3390/cells10020412
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author Salter, Brittany M.
Ju, Xiaotian
Sehmi, Roma
author_facet Salter, Brittany M.
Ju, Xiaotian
Sehmi, Roma
author_sort Salter, Brittany M.
collection PubMed
description Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5–10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strategies that target airway eosinophilia with corticosteroid-sparing benefits. A growing body of evidence shows that a balance between systemic differentiation and local tissue eosinophilopoietic processes driven by traffic and lung homing of bone marrow-derived hemopoietic progenitor cells (HPCs) are important components for the development of airway eosinophilia in asthma. Interleukin (IL)-5 is considered a critical and selective driver of terminal differentiation of eosinophils. Studies targeting IL-5 or IL-5R show that although mature and immature eosinophils are decreased within the airways, there is incomplete ablation, particularly within the bronchial tissue. Eotaxin is a chemoattractant for mature eosinophils and eosinophil-lineage committed progenitor cells (EoP), yet anti-CCR3 studies did not yield meaningful clinical outcomes. Recent studies highlight the role of epithelial cell-derived alarmin cytokines, IL-33 and TSLP, (Thymic stromal lymphopoietin) in progenitor cell traffic and local differentiative processes. This review provides an overview of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets. We will show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eosinophilia. Blocking lung homing and local eosinophilopoiesis through mediators upstream of this cascade may yield greater improvement in clinical outcomes.
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spelling pubmed-79204182021-03-02 Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma Salter, Brittany M. Ju, Xiaotian Sehmi, Roma Cells Review Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5–10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strategies that target airway eosinophilia with corticosteroid-sparing benefits. A growing body of evidence shows that a balance between systemic differentiation and local tissue eosinophilopoietic processes driven by traffic and lung homing of bone marrow-derived hemopoietic progenitor cells (HPCs) are important components for the development of airway eosinophilia in asthma. Interleukin (IL)-5 is considered a critical and selective driver of terminal differentiation of eosinophils. Studies targeting IL-5 or IL-5R show that although mature and immature eosinophils are decreased within the airways, there is incomplete ablation, particularly within the bronchial tissue. Eotaxin is a chemoattractant for mature eosinophils and eosinophil-lineage committed progenitor cells (EoP), yet anti-CCR3 studies did not yield meaningful clinical outcomes. Recent studies highlight the role of epithelial cell-derived alarmin cytokines, IL-33 and TSLP, (Thymic stromal lymphopoietin) in progenitor cell traffic and local differentiative processes. This review provides an overview of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets. We will show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eosinophilia. Blocking lung homing and local eosinophilopoiesis through mediators upstream of this cascade may yield greater improvement in clinical outcomes. MDPI 2021-02-16 /pmc/articles/PMC7920418/ /pubmed/33669458 http://dx.doi.org/10.3390/cells10020412 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Salter, Brittany M.
Ju, Xiaotian
Sehmi, Roma
Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title_full Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title_fullStr Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title_full_unstemmed Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title_short Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma
title_sort eosinophil lineage-committed progenitors as a therapeutic target for asthma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920418/
https://www.ncbi.nlm.nih.gov/pubmed/33669458
http://dx.doi.org/10.3390/cells10020412
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