Abstract
Original language | English |
---|---|
Pages (from-to) | 719-757 |
Number of pages | 39 |
Journal | Annual review of immunology |
Volume | 39 |
DOIs | |
Publication status | Published - 26 Apr 2021 |
Keywords
- IL-5
- biologic agents
- eosinophil
- eosinophil knockout
- eosinophil-associated diseases
- eosinophil-deficient mice
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In: Annual review of immunology, Vol. 39, 26.04.2021, p. 719-757.
Research output: Contribution to journal › Review article › Academic › peer-review
TY - JOUR
T1 - Eosinophil Knockout Humans: Uncovering the Role of Eosinophils through Eosinophil-Directed Biological Therapies
AU - Jacobsen, Elizabeth A.
AU - Jackson, David J.
AU - Heffler, Enrico
AU - Mathur, Sameer K.
AU - Bredenoord, Albert J.
AU - Pavord, Ian D.
AU - Akuthota, Praveen
AU - Roufosse, Florence
AU - Rothenberg, Marc E.
N1 - Funding Information: E.A.J. has received advisory board fees from AstraZeneca and speaker fees from GlaxoSmithKline (GSK). D.J.J. has received advisory board and speaker fees from AstraZeneca, GSK, Sanofi, Novartis, and Teva Pharmaceuticals. E.H. has received advisory board support from AstraZeneca, GSK, Novartis, Sanofi, Circassia, Stallergenes-Greer, and Nestlè Purina. S.K.M. has received consulting and speaker fees from AstraZeneca and GSK. A.J.B. has received research support from Nutricia, Bayer, Norgine, and SST and consulting/speaking fees from AstraZeneca, Alimentiv, Dr. Falk Pharma, Celgene, Arena Pharmaceuticals, Regeneron, Medtronic, and Laborie and has an equity interest in SST. In the last 5 years, I.D.P. has received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini, and GSK and payments for organizing educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford, United Kingdom. He is co–patent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer, and Insmed. In 2014–2015, he was an expert witness for a patent dispute involving AstraZeneca and Teva. P.A. has received research support from the National Institutes of Health; has received research support and consultancy fees from and has been on advisory boards for AstraZeneca and GSK; has received consultancy fees from Ambrx; receives royalties from UpToDate; and has received honoraria from WebMD/Medscape, AHK, Prime CME, Rock-pointe, MJH Life Sciences, and Vindico. F.R. is a consultant for GSK and AstraZeneca and receives royalties from UpToDate. M.E.R. is a consultant for Pulm One, Spoon Guru, Clostra-Bio, Serpin Pharm, Allakos, Celgene, AstraZeneca, Arena Pharmaceuticals, Ellodi Pharma, GSK, Sanofi/Regeneron, Guidepoint, and Suvretta Capital Management and has an equity interest in the first five listed and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate; M.E.R. is an inventor on patents owned by Cincinnati Children’s Hospital Medical Center. Funding Information: Shawna Hottinger, a medical writer employed by Cincinnati Children’s Hospital Medical Center, provided editorial assistance for this review. E.A.J. is supported by NIAID R01 AI145108, R21 AI132840, and R01 DK121330 and by the Mayo Foundation. E.A.J. would like to thank her late colleague Dr. James J. Lee, who created many of the strains mentioned in this manuscript and helped bring forth the idea that eosinophils have multiple roles in health and disease. A.J.B. is supported by the Vidi grant 91718300 from the Netherlands Organisation for Scientific Research NWO. F.R. is supported by the Belgian National Fund for Scientific Research (FNRS), grant numbers F 5/4/150/5 and FC 54372. M.E.R. is supported by NIH R01 AI045898, U19 AI070235, R01 AI057803, U54 AI117804, R01 AI124355, and R01 DK107502; the Campaign Urging Research for Eosinophilic Disease (CURED); and the Sunshine Charitable Foundation and its supporters and Denise and David Bunning. Funding Information: Shawna Hottinger, a medical writer employed by Cincinnati Children s Hospital Medical Center, provided editorial assistance for this review. E.A.J. is supported by NIAID R01 AI145108, R21 AI132840, and R01 DK121330 and by the Mayo Foundation. E.A.J. would like to thank her late colleague Dr. James J. Lee, who created many of the strains mentioned in this manuscript and helped bring forth the idea that eosinophils have multiple roles in health and disease. A.J.B. is supported by the Vidi grant 91718300 from the Netherlands Organisation for Scientific Research NWO.F.R. is supported by the BelgianNational Fund for Scientific Research (FNRS), grant numbers F 5/4/150/5 and FC 54372. M.E.R. is supported byNIH R01 AI045898, U19 AI070235, R01 AI057803, U54 AI117804, R01 AI124355, and R01 DK107502; the Campaign Urging Research for Eosinophilic Disease (CURED); and the Sunshine Charitable Foundation and its supporters and Denise and David Bunning. Publisher Copyright: © 2021 Annual Reviews Inc.. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/26
Y1 - 2021/4/26
N2 - The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.
AB - The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.
KW - IL-5
KW - biologic agents
KW - eosinophil
KW - eosinophil knockout
KW - eosinophil-associated diseases
KW - eosinophil-deficient mice
UR - http://www.scopus.com/inward/record.url?scp=85104994903&partnerID=8YFLogxK
U2 - https://doi.org/10.1146/annurev-immunol-093019-125918
DO - https://doi.org/10.1146/annurev-immunol-093019-125918
M3 - Review article
C2 - 33646859
SN - 0732-0582
VL - 39
SP - 719
EP - 757
JO - Annual review of immunology
JF - Annual review of immunology
ER -