Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4<SUP>+</SUP> cells

作者全名："Chen, Shuang; Li, Caihua; Tu, Zeng; Cai, Tao; Zhang, Xinying; Wang, Lei; Tian, Ruoyuan; Huang, Jinglan; Gong, Yuxuan; Yang, Xiaotong; Wu, Zetong; He, Sirong; He, Wenyan; Wang, Dan"

作者地址："[Chen, Shuang; Cai, Tao; Wang, Lei; He, Wenyan] Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, Chongqing, Peoples R China; [Li, Caihua; Zhang, Xinying; Tian, Ruoyuan; Huang, Jinglan; He, Sirong] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China; [Li, Caihua; Zhang, Xinying; Tian, Ruoyuan; Huang, Jinglan; He, Sirong] Chongqing Med Univ, Coll Basic Med, Chongqing Key Lab Basic & Translat Res Tumor Immu, Chongqing, Peoples R China; [Tu, Zeng] Chongqing Med Univ, Coll Basic Med, Dept Pathogen Biol, Chongqing, Peoples R China; [Gong, Yuxuan; Yang, Xiaotong; Wu, Zetong] Chongqing Med Univ, Int Med Coll, Chongqing, Peoples R China; [Wang, Dan] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China"

通信作者："He, WY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, Chongqing, Peoples R China.; Wang, D (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001184576900001

JCR分区：Q1

影响因子：5.6

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：atopic dermatitis; JAK/STAT; baricitinib; th2; autoimmune diseases

摘要："As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD."

基金机构："Program of National Natural Science Foundation of China [31971054, 82003380, 82273533]; Natural Science Foundation of Chongqing, China [CSTB2022NSCQ-MSX1063, cstc20JCYJ-MSXMX0110]; Program of China Postdoctoral Science Foundation [2023MD744158]; Special Project of Postdoctoral Research Program of Chongqing [2022CQBSHTB3004]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202200436]; Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing [20210120]; CQMU Program for Youth Innovation in Future Medicine [W0100]; Research foundation of the first affiliated hospital of Chongqing Medical University, China"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was sponsored by the Program of National Natural Science Foundation of China (Nos 31971054, 82003380, and 82273533), the Natural Science Foundation of Chongqing, China (Nos CSTB2022NSCQ-MSX1063 and cstc20JCYJ-MSXMX0110), the Program of China Postdoctoral Science Foundation (No. 2023MD744158), the Special Project of Postdoctoral Research Program of Chongqing (No. 2022CQBSHTB3004), the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202200436), the Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing (No. 20210120), the CQMU Program for Youth Innovation in Future Medicine (No. W0100), and the research foundation of the first affiliated hospital of Chongqing Medical University, China."