CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation

Allergic asthma is a chronic inflammatory disorder associated with airway hyperreactivity (AHR) whose global prevalence is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) and T helper 2 (T(H)2) cells are producers of type 2 cytokines, which may contribute to development of AHR....

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Autores principales: Shafiei-Jahani, Pedram, Helou, Doumet Georges, Hurrell, Benjamin P., Galle-Treger, Lauriane, Howard, Emily, Quach, Christine, Painter, Jacob D., Fung, Marshall, Lo, Richard, Allayee, Hooman, Akbari, Omid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225558/
https://www.ncbi.nlm.nih.gov/pubmed/33731828
http://dx.doi.org/10.1038/s41385-021-00388-5
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author Shafiei-Jahani, Pedram
Helou, Doumet Georges
Hurrell, Benjamin P.
Galle-Treger, Lauriane
Howard, Emily
Quach, Christine
Painter, Jacob D.
Fung, Marshall
Lo, Richard
Allayee, Hooman
Akbari, Omid
author_facet Shafiei-Jahani, Pedram
Helou, Doumet Georges
Hurrell, Benjamin P.
Galle-Treger, Lauriane
Howard, Emily
Quach, Christine
Painter, Jacob D.
Fung, Marshall
Lo, Richard
Allayee, Hooman
Akbari, Omid
author_sort Shafiei-Jahani, Pedram
collection PubMed
description Allergic asthma is a chronic inflammatory disorder associated with airway hyperreactivity (AHR) whose global prevalence is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) and T helper 2 (T(H)2) cells are producers of type 2 cytokines, which may contribute to development of AHR. In this study, we explore the potential of CD52-targeted depletion of type 2 immune cells for treating allergic AHR. Here we showed that anti-CD52 therapy can prevent and remarkably reverse established IL-33-induced AHR by reducing airway resistance and alleviating lung inflammation. We further show that CD52 depletion prevents and treats allergic AHR induced by clinically relevant allergens such as Alternaria alternata and House Dust Mite (HDM). Importantly, we leverage various humanized mice models of AHR to show new therapeutic applications for Alemtuzumab, an anti-CD52 depleting antibody that is currently FDA-approved for treatment of multiple sclerosis. Our results demonstrate that CD52 depletion is a viable therapeutic option for reduction of pulmonary inflammation, abrogation of eosinophilia, improvement of lung function, and thus treatment of allergic AHR. Taken together, our data suggest that anti-CD52 depleting monoclonal antibodies, such as Alemtuzumab, can serve as viable therapeutic drugs for amelioration of T(H)2 and ILC2 dependent AHR.
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spelling pubmed-82255582021-09-17 CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation Shafiei-Jahani, Pedram Helou, Doumet Georges Hurrell, Benjamin P. Galle-Treger, Lauriane Howard, Emily Quach, Christine Painter, Jacob D. Fung, Marshall Lo, Richard Allayee, Hooman Akbari, Omid Mucosal Immunol Article Allergic asthma is a chronic inflammatory disorder associated with airway hyperreactivity (AHR) whose global prevalence is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) and T helper 2 (T(H)2) cells are producers of type 2 cytokines, which may contribute to development of AHR. In this study, we explore the potential of CD52-targeted depletion of type 2 immune cells for treating allergic AHR. Here we showed that anti-CD52 therapy can prevent and remarkably reverse established IL-33-induced AHR by reducing airway resistance and alleviating lung inflammation. We further show that CD52 depletion prevents and treats allergic AHR induced by clinically relevant allergens such as Alternaria alternata and House Dust Mite (HDM). Importantly, we leverage various humanized mice models of AHR to show new therapeutic applications for Alemtuzumab, an anti-CD52 depleting antibody that is currently FDA-approved for treatment of multiple sclerosis. Our results demonstrate that CD52 depletion is a viable therapeutic option for reduction of pulmonary inflammation, abrogation of eosinophilia, improvement of lung function, and thus treatment of allergic AHR. Taken together, our data suggest that anti-CD52 depleting monoclonal antibodies, such as Alemtuzumab, can serve as viable therapeutic drugs for amelioration of T(H)2 and ILC2 dependent AHR. 2021-03-17 2021-07 /pmc/articles/PMC8225558/ /pubmed/33731828 http://dx.doi.org/10.1038/s41385-021-00388-5 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shafiei-Jahani, Pedram
Helou, Doumet Georges
Hurrell, Benjamin P.
Galle-Treger, Lauriane
Howard, Emily
Quach, Christine
Painter, Jacob D.
Fung, Marshall
Lo, Richard
Allayee, Hooman
Akbari, Omid
CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title_full CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title_fullStr CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title_full_unstemmed CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title_short CD52-targeted depletion by Alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
title_sort cd52-targeted depletion by alemtuzumab ameliorates allergic airway hyperreactivity and lung inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225558/
https://www.ncbi.nlm.nih.gov/pubmed/33731828
http://dx.doi.org/10.1038/s41385-021-00388-5
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