ResearchIn-Press PreviewImmunologyPulmonology Free access | 10.1172/jci.insight.124710
Find articles by Lee, Y. in: JCI | PubMed | Google Scholar
Find articles by Reader, B. in: JCI | PubMed | Google Scholar
Find articles by Herman, D. in: JCI | PubMed | Google Scholar
Find articles by
Streicher, A.
in:
JCI
|
PubMed
|
Google Scholar
|
Find articles by
Englert, J.
in:
JCI
|
PubMed
|
Google Scholar
|
Find articles by
Ziegler, M.
in:
JCI
|
PubMed
|
Google Scholar
|
Find articles by Chung, S. in: JCI | PubMed | Google Scholar
Find articles by Karpurapu, M. in: JCI | PubMed | Google Scholar
Find articles by Park, G. in: JCI | PubMed | Google Scholar
Find articles by Christman, J. in: JCI | PubMed | Google Scholar
Find articles by
Ballinger, M.
in:
JCI
|
PubMed
|
Google Scholar
|
First published January 22, 2019 - More info
Allergic eosinophilic asthma is a chronic condition causing airway remodeling resulting in lung dysfunction. We observed that expression of Sirtuin 2 (Sirt2), a histone deacetylase, regulates the recruitment of eosinophils after sensitization and challenge with a triple-antigen: dust mite, ragweed and Aspergillus fumigatus (DRA). Our data demonstrate that IL-4 regulates the expression of Sirt2 isoform 3/5. Pharmacological inhibition of Sirt2 by AGK2 resulted in diminished cellular recruitment, decreased CCL17/TARC, and reduced goblet cell hyperplasia. YM1 and Fizz1 expression was reduced in AGK2-treated, IL-4-stimulated lung macrophages in vitro as well as in lung macrophages from AGK2-DRA challenged mice. Conversely, overexpression of Sirt2 resulted in increased cellular recruitment, CCL17 production, and goblet cell hyperplasia following DRA challenge. Sirt2 isoform 3/5 was upregulated in primary human alveolar macrophages following IL-4 and AGK2 treatment resulted in reduced CCL17 and markers of alternative activation. These gain-of-function and loss-of-function studies indicate that Sirt2 could be developed as a treatment for eosinophilic asthma.