Stürner Klarissa Hanja, Verse Nina, Yousef Sara, Martin Roland, Sospedra Mireia
Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (INIMS) and Clinic for Neurology, Center for Molecular Neurobiology, Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany.
Eur J Immunol. 2014 Apr;44(4):1200-12. doi: 10.1002/eji.201343629. Epub 2014 Feb 16.
Interferon-gamma producing CD4(+) T (Th1) cells and IL-17-producing CD4(+) T (Th17) cells are involved in the pathogenesis of several autoimmune diseases including multiple sclerosis. Therefore, the development of treatment strategies controlling the generation and expansion of these effector cells is of high interest. Frankincense, the resin from trees of the genus Boswellia, and particularly its prominent bioactive compound acetyl-11-keto-β-boswellic acid (AKBA), have potent anti-inflammatory properties. Here, we demonstrate that AKBA is able to reduce the differentiation of human CD4(+) T cells to Th17 cells, while slightly increasing Th2- and Treg-cell differentiation. Furthermore, AKBA reduces the IL-1β-triggered IL-17A release of memory Th17 cells. AKBA may affect IL-1β signaling by preventing IL-1 receptor-associated kinase 1 phosphorylation and subsequently decreasing STAT3 phosphorylation at Ser727, which is required for Th17-cell differentiation. The effects of AKBA on Th17 differentiation and IL-17A release make the compound a good candidate for potential treatment of Th17-driven diseases.
产生干扰素-γ的CD4(+) T（Th1）细胞和产生白细胞介素-17的CD4(+) T（Th17）细胞参与包括多发性硬化症在内的多种自身免疫性疾病的发病机制。因此，开发控制这些效应细胞生成和扩增的治疗策略备受关注。乳香，即乳香属树木的树脂，尤其是其主要生物活性化合物乙酰-11-酮-β-乳香酸（AKBA），具有强大的抗炎特性。在此，我们证明AKBA能够减少人CD4(+) T细胞向Th17细胞的分化，同时略微增加Th2细胞和调节性T细胞（Treg）的分化。此外，AKBA可降低白细胞介素-1β（IL-1β）触发的记忆性Th17细胞释放白细胞介素-17A（IL-17A）。AKBA可能通过阻止IL-1受体相关激酶1磷酸化并随后降低Th17细胞分化所需的Ser727位点的信号转导和转录激活因子3（STAT3）磷酸化来影响IL-1β信号传导。AKBA对Th17分化和IL-17A释放的作用使其成为治疗Th17驱动疾病的潜在良好候选药物。
