Pearson Ryan M, Casey Liam M, Hughes Kevin R, Miller Stephen D, Shea Lonnie D
Department of Biomedical Engineering, University of Michigan, 1119 Carl A. Gerstacker Building, 2200 Bonisteel Boulevard, Ann Arbor, MI 48109-2099, USA.
Department of Chemical Engineering, University of Michigan, 2300 Hayward Ave., Ann Arbor, MI 48105, USA.
Adv Drug Deliv Rev. 2017 May 15;114:240-255. doi: 10.1016/j.addr.2017.04.005. Epub 2017 Apr 14.
Technologies that induce antigen-specific immune tolerance by mimicking naturally occurring mechanisms have the potential to revolutionize the treatment of many immune-mediated pathologies such as autoimmunity, allograft rejection, and allergy. The immune system intrinsically has central and peripheral tolerance pathways for eliminating or modulating antigen-specific responses, which are being exploited through emerging technologies. Antigen-specific tolerogenic responses have been achieved through the functional reprogramming of antigen-presenting cells or lymphocytes. Alternatively, immune privileged sites have been mimicked using biomaterial scaffolds to locally suppress immune responses and promote long-term allograft survival. This review describes natural mechanisms of peripheral tolerance induction and the various technologies being developed to achieve antigen-specific immune tolerance in vivo. As currently approved therapies are non-specific and carry significant associated risks, these therapies offer significant progress towards replacing systemic immune suppression with antigen-specific therapies to curb aberrant immune responses.
通过模拟自然发生机制来诱导抗原特异性免疫耐受的技术，有可能彻底改变许多免疫介导疾病的治疗方式，如自身免疫性疾病、同种异体移植排斥反应和过敏。免疫系统本身具有中枢和外周耐受途径，用于消除或调节抗原特异性反应，而新兴技术正在利用这些途径。通过抗原呈递细胞或淋巴细胞的功能重编程已实现了抗原特异性致耐受性反应。另外，已利用生物材料支架模拟免疫赦免部位，以局部抑制免疫反应并促进同种异体移植的长期存活。本综述描述了外周耐受诱导的自然机制以及为在体内实现抗原特异性免疫耐受而正在开发的各种技术。由于目前批准的疗法是非特异性的且伴有重大相关风险，因此这些疗法朝着用抗原特异性疗法取代全身免疫抑制以抑制异常免疫反应取得了重大进展。
