机构：[1]Department of Pulmonary and Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China[4]Institute Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai, China[5]Department of Pulmonary and Critical Care Medicine, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[6]Department of Thoracic Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Aims: Asthma is characterized by chronic inflammation and airway hyperresponsiveness (AHR). It is controllable, but not curable. Ubiquitin-specific peptidase 4 (USP4) has been verified as a regulator of regulatory T (Treg) cells and Th17 cells in vitro. In this study, we aim to investigate whether USP4 could serve as a therapeutic target for asthma. Main methods: Age-matched USP4 wild-type and knockout mice received an intraperitoneal injection of 100 mu g ovalbumin (OVA) mixed in 2 mg aluminum hydroxide in 1 x PBS on days 0, 7 and 14. On days 21 to 27, the mice were challenged with aerosolized 1% OVA in 1 x PBS for 30 min. Tissue histology, ELISA and flow cytometry were applied 24 h after the last OVA challenge. Key findings: USP4 deficiency protected mice from OVA-induced AHR and decreased the production of several inflammatory cytokines in T cells in vivo. Compared to the lung cells isolated from WT mice, Usp4-/- lung cells decreased secretion of IL-4, IL-13 and IL-17A upon stimulation in vitro. Meanwhile, the percentage of CD4+Foxp3+ Treg cells was elevated, with more CCR6+Foxp3+ Treg cells accumulating in the lungs of OVAchallenged USP4 deficient mice than in their wild-type counterparts. Treatment with the USP4 inhibitor, Vialinin A, reduced inflammatory cell infiltration in the lungs of OVA-challenged mice in vivo. Significance: We found USP4 deficiency contributes to attenuated airway inflammation and AHR in allergeninduced murine asthma, and Vialinin A treatment alleviates asthma pathogenesis and may serve as a promising therapeutic target for asthma.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81500011, 81770025, 81970020]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|3 区医学
小类|3 区医学：研究与实验3 区药学
最新[2023]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区药学
JCR分区：
出版当年[2019]版：
Q2MEDICINE, RESEARCH & EXPERIMENTALQ2PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者机构：[1]Department of Pulmonary and Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pulmonary and Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China[3]Shanghai Institute of Immunology, Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China[*1]No.197, Ruijin Er Road, Shanghai 200025, China.
推荐引用方式(GB/T 7714)：
Hou Xiaoxia,Zhu Fangming,Ni Yingmeng,et al.USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response[J].LIFE SCIENCES.2021,281:doi:10.1016/j.lfs.2021.119720.
APA：
Hou, Xiaoxia,Zhu, Fangming,Ni, Yingmeng,Chen, Tiantian,Du, Juan...&Shi, Guochao.(2021).USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response.LIFE SCIENCES,281,
MLA：
Hou, Xiaoxia,et al."USP4 is pathogenic in allergic airway inflammation by inhibiting regulatory T cell response".LIFE SCIENCES 281.(2021)
医学