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....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2021
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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. |
format | Online Article Text |
id | pubmed-8225558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
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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