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

ABSTRACT: 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_H2) 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 show 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. 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_H2- and ILC2-dependent AHR.

SUBMITTER: Shafiei-Jahani P

PROVIDER: S-EPMC8225558 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Shafiei-Jahani Pedram P Helou Doumet Georges DG Hurrell Benjamin P BP Galle-Treger Lauriane L Howard Emily E Quach Christine C Painter Jacob D JD Fung Marshall M Lo Richard R Allayee Hooman H Akbari Omid O

Mucosal immunology 20210317 4

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<sub>H</sub>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 show that anti-CD52 therapy can prevent and remarkably reverse es ...[more]

PMID: 33731828

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Dataset Information

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

Publications

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

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