Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities.

Abstract

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.

• Authors: Li-Yen Lee, Geena Suet Yin Hew, Meenu Mehta, Shakti D Shukla, Saurabh Satija, Navneet Khurana, Krishnan Anand, Harish Dureja, Sachin Kumar Singh, Vijay Mishra, Pankaj Kumar Singh, Monica Gulati, Parteek Prasher, Alaa A A Aljabali, Murtaza M Tambuwala, Lakshmi Thangavelu, Jithendra Panneerselvam, Gaurav Gupta, Flavia C Zacconi, Madhur Shastri, Niraj Kumar Jha, Dikaia Xenaki, Ronan MacLoughlin, Brian G Oliver, Dinesh Kumar Chellappan, Kamal Dua
• Journal: Life sciences (Life Sci) Vol. 267 Pg. 118973 (Feb 15 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33400932 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines

Topics

• Animals
• Cytokines (immunology, metabolism)
• Eosinophils (drug effects, immunology, metabolism)
• Humans
• Lung (metabolism, pathology)
• Respiration Disorders (immunology, metabolism, physiopathology)
• Respiratory Tract Diseases (immunology, metabolism, physiopathology)
• Th2 Cells (immunology, metabolism)