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
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 in...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1324892/full |
| _version_ | 1797291914992549888 |
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| author | Shuang Chen Caihua Li Caihua Li Zeng Tu Tao Cai Xinying Zhang Xinying Zhang Lei Wang Ruoyuan Tian Ruoyuan Tian Jinglan Huang Jinglan Huang Yuxuan Gong Xiaotong Yang Zetong Wu Sirong He Sirong He Wenyan He Dan Wang |
| author_facet | Shuang Chen Caihua Li Caihua Li Zeng Tu Tao Cai Xinying Zhang Xinying Zhang Lei Wang Ruoyuan Tian Ruoyuan Tian Jinglan Huang Jinglan Huang Yuxuan Gong Xiaotong Yang Zetong Wu Sirong He Sirong He Wenyan He Dan Wang |
| author_sort | Shuang Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T19:44:39Z |
| format | Article |
| id | doaj.art-a35e60e28caf4a85a20da0baf3e27aff |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-07T19:44:39Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a35e60e28caf4a85a20da0baf3e27aff2024-02-29T04:33:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-02-011510.3389/fphar.2024.13248921324892Off-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+ cellsShuang Chen0Caihua Li1Caihua Li2Zeng Tu3Tao Cai4Xinying Zhang5Xinying Zhang6Lei Wang7Ruoyuan Tian8Ruoyuan Tian9Jinglan Huang10Jinglan Huang11Yuxuan Gong12Xiaotong Yang13Zetong Wu14Sirong He15Sirong He16Wenyan He17Dan Wang18Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Pathogen Biology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaInternational Medical College, Chongqing Medical University, Chongqing, ChinaInternational Medical College, Chongqing Medical University, Chongqing, ChinaInternational Medical College, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaAs 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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1324892/fullatopic dermatitisJAK/STATbaricitinibth2autoimmune diseases |
| spellingShingle | Shuang Chen Caihua Li Caihua Li Zeng Tu Tao Cai Xinying Zhang Xinying Zhang Lei Wang Ruoyuan Tian Ruoyuan Tian Jinglan Huang Jinglan Huang Yuxuan Gong Xiaotong Yang Zetong Wu Sirong He Sirong He Wenyan He Dan Wang 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 Frontiers in Pharmacology atopic dermatitis JAK/STAT baricitinib th2 autoimmune diseases |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | atopic dermatitis JAK/STAT baricitinib th2 autoimmune diseases |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1324892/full |
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