IgD Mab Technology (IMT) Group, Sydney, NSW, 2113, Australia.
Inflamm Res. 2020 Sep;69(9):813-824. doi: 10.1007/s00011-020-01374-6. Epub 2020 Jun 26.
It paradoxically seems counter-intuitive to consider treatments that activate the immune systems as a method to treat autoimmune diseases and chronic inflammations when these inflammatory conditions are themselves manifested by dysregulated activations of the immune responses. However, according to Newton's Third-Law of fundamental physics which formally states "For every action, there is an equal and opposite reaction", it can be reasonably argued that "For every activated pro-inflammatory response, there is an opposite and intrinsic anti-inflammatory response to follow." Therefore, harnessing these intrinsic self-regulated negative-feedbacks of anti-inflammatory and tolerogenic responses by activating the immune systems represents a novel therapeutic paradigm.
This review endeavoured to examine and discuss the current clinical and experimental evidences and therapeutic potentials of activating the innate and adaptive immune systems via their classical cell receptors, namely Toll-like receptors (TLRs), T-cell receptors (TCRs), and B cell receptors (BCRs), to modulate and suppress pathogenic inflammations.
The evidence presented in this review illustrated the therapeutic potentials and the caveats of recent approaches and advances in harnessing this unorthodox therapeutic paradigm in the treatments of autoimmune diseases, allergic and chronic inflammations. It highlighted the promising potentials of targeting BCR-activated tolergenic responses as a new approach in this new therapeutic paradigm.
当自身免疫性疾病和慢性炎症等炎症状态本身表现为免疫反应失调激活时,将激活免疫系统的治疗方法视为治疗这些疾病的方法似乎有些违背直觉。然而,根据牛顿第三运动定律,即“对于每一个作用,都有一个大小相等、方向相反的反作用”,可以合理地认为“对于每一个激活的促炎反应,都会有一个相反的内在抗炎反应随之而来。”因此,通过激活免疫系统来利用这些内在的自我调节抗炎和耐受反应的负反馈,代表了一种新的治疗范例。
本综述旨在检查和讨论通过其经典细胞受体(即 Toll 样受体 (TLR)、T 细胞受体 (TCR) 和 B 细胞受体 (BCR))激活先天和适应性免疫系统以调节和抑制致病性炎症的当前临床和实验证据以及治疗潜力。
本综述中提出的证据说明了在治疗自身免疫性疾病、过敏和慢性炎症方面,利用这种非传统治疗范例的最新方法和进展的治疗潜力和注意事项。它强调了靶向 BCR 激活的耐受反应作为这种新治疗范例中的一种新方法的有前途的潜力。