Figueiredo Ana Sofia, Schumacher Anne
Medical Faculty, Institute for Experimental Internal Medicine, Otto-von-Guericke University, Magdeburg, Germany.
Medical Faculty, Institute for Experimental Obstetrics and Gynecology, Otto-von-Guericke University, Magdeburg, Germany.
Immunology. 2016 May;148(1):13-21. doi: 10.1111/imm.12595.
T helper type 17 (Th17) and regulatory T (Treg) cells are active players in the establishment of tolerance and defence. These attributes of the immune system enmesh to guarantee the right level of protection. The healthy immune system, on the one hand, recognizes and eliminates dangerous non-self pathogens and, on the other hand, protects the healthy self. However, there are circumstances where this fine balance is disrupted. In fact, in situations such as in pregnancy, the foreign fetal antigens challenge the maternal immune system and Treg cells will dominate Th17 cells to guarantee fetal survival. In other situations such as autoimmunity, where the Th17 responses are often overwhelming, the immune system shifts towards an inflammatory profile and attacks the healthy tissue from the self. Interestingly, autoimmune patients have meliorating symptoms during pregnancy. This connects with the antagonist role of Th17 and Treg cells, and their specific profiles during these two immune challenging situations. In this review, we put into perspective the Th17/Treg ratio during pregnancy and autoimmunity, as well as in pregnant women with autoimmune conditions. We further review existing systems biology approaches that study specific mechanisms of these immune cells using mathematical modelling and we point out possible future directions of investigation. Understanding what maintains or disrupts the balance between these two opponent yet reciprocal cells in healthy physiological settings, sheds light into the development of innovative pharmacological approaches to fight pregnancy loss and autoimmunity.
17型辅助性T细胞(Th17)和调节性T细胞(Treg)在建立免疫耐受和免疫防御过程中发挥着积极作用。免疫系统的这些特性相互交织,以确保适当的保护水平。健康的免疫系统一方面识别并清除危险的非自身病原体,另一方面保护健康的自身组织。然而,在某些情况下,这种微妙的平衡会被打破。事实上,在怀孕等情况下,外来的胎儿抗原会挑战母体免疫系统,Treg细胞将占主导地位,抑制Th17细胞,以确保胎儿存活。在其他情况下,如自身免疫性疾病,Th17反应往往占主导,免疫系统会转向炎症状态并攻击自身的健康组织。有趣的是,自身免疫性疾病患者在怀孕期间症状会有所缓解。这与Th17和Treg细胞的拮抗作用以及它们在这两种免疫挑战情况下的特定状态有关。在这篇综述中,我们阐述了怀孕和自身免疫性疾病期间,以及患有自身免疫性疾病的孕妇体内Th17/Treg细胞的比例。我们还进一步综述了现有的系统生物学方法,这些方法利用数学模型研究这些免疫细胞的具体机制,并指出了未来可能的研究方向。了解在健康生理环境中是什么维持或破坏了这两种相互对立却又相互作用的细胞之间的平衡,有助于开发创新的药理学方法来对抗流产和自身免疫性疾病。