Beijing Hospital of Traditional Chinese Medicine, Affiliated With Capital Medical University, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, No.23 Mei shu guan Back Road, DongCheng District, Beijing, 100010, China.
Beijing Hospital of Traditional Chinese Medicine, Affiliated With Capital Medical University, Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing Institute of Traditional Chinese Medicine, No.23 Mei shu guan Back Road, DongCheng District, Beijing, 100010, China.
Mol Immunol. 2018 Sep;101:386-395. doi: 10.1016/j.molimm.2018.07.011. Epub 2018 Jul 29.
Indirubin (IR) is a bisindole compound extracted from the leaves of Chinese herb Indigo Naturalis. Indigo Naturalis has been widely used in traditional Chinese medicine to treat inflammatory and autoimmune diseases. Psoriasis is a chronic immune-mediated inflammatory skin disease in which γδ T cells play an important role. This study aims to determine the immunoregulatory effects and the underlying mechanisms of Indirubin in psoriasis-related inflammatory responses.
BALB/c mice with imiquimod (IMQ)-induced psoriasis-like dermatitis were treated with saline (Model), 1 mg/kg methotrexate (MTX) that serves as a positive control, or 12.5, 25 and 50 mg/kg Indirubin(IR) intragastrically. Keratinocytes proliferation, inflammatory cells infiltration, the expression of inflammatory cytokines and Jak/Stat pathway-related proteins in the skin lesion were examined. The abundance of γδ T cells in lymph nodes and spleen was determined by flow cytometry. The IL-17 expression and secretion, and the activation of Jak3/Stat3 pathways in in vitro cultured γδ T cell were tested.
Indirubin ameliorated keratinocyte proliferation, reduced the infiltration of CD3 T cells, IL-17 A-producing γδ T cells, and CD11b neutrophils, inhibited the mRNA expression of Il1, Il6, Il23, Il17a and Il22, and the protein expression of Jak/Stat pathway-related molecules in the skin lesion. Indirubin also reduced the abundance of γδ T cell and CCR6 γδ T cells (the major IL-17 A producer) in spleen and lymph nodes. In cultured γδ T cells, Indirubin inhibited the mRNA expression of Il17a and Ifng, and the secretion of IL-17 A, while suppressed the activation of Jak3/Stat3 pathways.
Indirubin alleviates IMQ-induced psoriasis-like dermatitis mainly through reducing the inflammatory responses mediated by IL-17 A-producing γδ T cells involving Jak3/Stat3 activation. Our results highlighted the novel mechanisms by which Indirubin ameliorates psoriasis-related inflammatory responses, supporting its therapeutic potential.
靛玉红（IR）是从中药青黛叶中提取的双吲哚化合物。青黛在传统中药中被广泛用于治疗炎症性和自身免疫性疾病。银屑病是一种慢性免疫介导的炎症性皮肤病，其中γδ T 细胞发挥重要作用。本研究旨在确定靛玉红在银屑病相关炎症反应中的免疫调节作用及其潜在机制。
用咪喹莫特（IMQ）诱导银屑病样皮炎的 BALB/c 小鼠用生理盐水（模型）、1mg/kg 甲氨蝶呤（MTX）（阳性对照）或 12.5、25 和 50mg/kg 靛玉红（IR）灌胃治疗。检测皮肤病变中角质形成细胞增殖、炎症细胞浸润、炎症细胞因子表达和 Jak/Stat 通路相关蛋白。用流式细胞术测定淋巴结和脾中 γδ T 细胞的丰度。检测体外培养的 γδ T 细胞中 IL-17 的表达和分泌以及 Jak3/Stat3 通路的激活。
靛玉红改善了角质形成细胞增殖，减少了 CD3 T 细胞、IL-17A 产生的 γδ T 细胞和 CD11b 中性粒细胞的浸润，抑制了皮肤病变中 Il1、Il6、Il23、Il17a 和 Il22 的 mRNA 表达以及 Jak/Stat 通路相关分子的蛋白表达。靛玉红还减少了脾和淋巴结中 γδ T 细胞和 CCR6 γδ T 细胞（主要的 IL-17A 产生细胞）的丰度。在培养的 γδ T 细胞中，靛玉红抑制了 Il17a 和 Ifng 的 mRNA 表达和 IL-17A 的分泌，同时抑制了 Jak3/Stat3 通路的激活。
靛玉红通过减少由 IL-17A 产生的 γδ T 细胞介导的炎症反应来缓解 IMQ 诱导的银屑病样皮炎，涉及 Jak3/Stat3 激活。我们的结果强调了靛玉红改善银屑病相关炎症反应的新机制，支持其治疗潜力。
