Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Lancet. 2013 Aug 31;382(9894):819-31. doi: 10.1016/S0140-6736(13)60954-X.
Systemic lupus erythematosus, Sjögren's syndrome, and dermatomyositis are systemic autoimmune diseases that develop after environmental triggering of genetically susceptible individuals. The precise cellular and molecular mechanisms leading to autoimmune disease, and what factors determine which organs are involved, remain poorly understood. Recent insights into genetic susceptibility now make obvious that environmental triggers often act via cellular pathways containing disease-associated polymorphisms. In the breaking of tolerance, the initiating tissue--including dendritic cells--provides a decisive microenvironment that affects immune-cell differentiation, leading to activation of adaptive immunity. Type 1 interferon produced by innate immune cells has a central role in systemic autoimmunity and activates B cells and T cells. In turn, B-cell-derived autoantibodies stimulate dendritic cells to produce type 1 interferon; thus, a positive feedforward loop is formed that includes both the innate and adaptive systems. New treatments could simultaneously and specifically target several such vital pathways in autoimmunity.
系统性红斑狼疮、干燥综合征和皮肌炎是系统性自身免疫性疾病，在遗传易感个体的环境触发后发展而来。导致自身免疫疾病的确切细胞和分子机制，以及哪些因素决定哪些器官受累，仍知之甚少。最近对遗传易感性的深入了解表明，环境触发因素通常通过含有疾病相关多态性的细胞途径起作用。在耐受打破中，起始组织——包括树突状细胞——提供了一个决定性的微环境，影响免疫细胞的分化，导致适应性免疫的激活。固有免疫细胞产生的 1 型干扰素在系统性自身免疫中具有核心作用，并激活 B 细胞和 T 细胞。反过来，B 细胞衍生的自身抗体刺激树突状细胞产生 1 型干扰素；因此，形成了一个正反馈环，其中包括先天和适应性系统。新的治疗方法可以同时和特异性地针对自身免疫中的几个这样的重要途径。
