Table1_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.XLSX

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.

特应性皮炎（atopic dermatitis, AD）是一类伴随免疫系统紊乱的炎症性疾病，其细胞因子紊乱与JAK-STAT信号通路的异常激活密切相关。JAK-STAT信号通路与AD发病机制的关键相关性，为JAK抑制剂的研发提供了坚实的理论依据。巴瑞替尼（Baricitinib）是一种小分子口服JAK抑制剂，已被证实可在包括AD在内的多种疾病中抑制JAK-STAT信号传导；目前我国已将其用于超适应症用药。然而，其在我国人群中的疗效及作用机制鲜有报道。本研究发现，中重度AD患者的免疫状态呈过度激活状态。在49个已知免疫治疗靶点中，AD患者淋巴细胞中的JAK1与JAK2基因显著上调，且该现象与中重度AD患者的症状严重程度密切相关。巴瑞替尼可通过调控MAPK、mTOR及PI3K-Akt信号通路，抑制Th2细胞亚群的激活与Th2型细胞因子的分泌，从而改善中重度AD患者的免疫高反应性与临床症状，为巴瑞替尼超适应症治疗中重度AD的临床应用提供了重要的理论基础。