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조회158

이현승Hyun-Seung Lee

서울대학교병원

Exp. Mol. Med., Dec 13 2024, | https://doi.org/10.1038/s12276-024-01367-z Essential role of Card11 in airway hyperresponsiveness in high-fat diet-induced obese mice

Hyun-Seung Lee ¹, Byung-Keun Kim ², Suh-Young Lee ³, Hyuktae Kwon ⁴ and Heung-Woo Park ^3,5,*

¹Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
²Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
³Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
⁴Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
⁵Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

^*Corresponding author: correspondence to Heung-Woo Park

Abstract

A high-fat diet (HFD) can induce airway hyperresponsiveness (AHR) in obese mice, independent of allergic sensitization. This study aimed to identify the key molecules related to AHR in HFD-induced obese mice. In a cluster analysis of time series gene expression in the adipose and lung tissues of HFD-induced obese mice, we identified the Caspase Recruitment Domain Family Member 11 (Card11) gene as an essential molecule. We measured CARD11 expression in peripheral blood mononuclear cells (PBMCs) from obese individuals with asthma and performed Card11 signal inhibition in HFD-induced obese mice via Card11 siRNA. Card11 expression was significantly increased in M1 macrophages (IL-1β⁺CD11c⁺CD206^- in CD11b⁺) in adipose tissue and in ILC3s (RORγt⁺ in IL7R⁺ of Lin^-) in lung tissue from HFD-induced obese mice. In addition, CARD11⁺ populations among ILC3s and LPS-stimulated IL-1β⁺CD16⁺ monocytes from the PBMCs of obese individuals with asthma were significantly greater than those from obese controls or nonobese individuals with asthma. AHR in HFD-induced obese mice disappeared when we inhibited the Card11 signaling pathway by administering Card11 siRNA during the first or last seven weeks of the 13-week HFD feeding. Finally, we confirmed that Card11 siRNA decreased the number of M1 macrophages in adipose tissue and the number of ILC3s in lung tissue in vitro. Card11 significantly contributes to the development of AHR in HFD-induced obese mice by affecting immune cells in both adipose and lung tissues. The middle stage of HFD feeding seemed to be critical for these processes.

논문정보

형식Research article
게재일2024년 12월 (BRIC 등록일 2025-01-21)
연구진국내 연구진
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