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+ cells

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

doi:10.3389/fphar.2024.1324892

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⁺ cells

Front Pharmacol. 2024 Feb 29:15:1324892. doi: 10.3389/fphar.2024.1324892. eCollection 2024.

Authors

Shuang Chen^#¹, Caihua Li^#^{2

3}, Zeng Tu⁴, Tao Cai¹, Xinying Zhang^{2

3}, Lei Wang¹, Ruoyuan Tian^{2

3}, Jinglan Huang^{2

3}, Yuxuan Gong⁵, Xiaotong Yang⁵, Zetong Wu⁵, Sirong He^{2

3}, Wenyan He¹, Dan Wang⁶

Affiliations

¹ Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
³ Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
⁴ Department of Pathogen Biology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.
⁵ International Medical College, Chongqing Medical University, Chongqing, China.
⁶ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

^# Contributed equally.

Abstract

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.

Keywords: JAK/STAT; atopic dermatitis; autoimmune diseases; baricitinib; th2.

Grants and funding

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.