School of Medicine, Faculty of Medicine and Biomedical Sciences, University of Queensland, St Lucia, QLD, Australia.
University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
Front Immunol. 2021 Jul 16;12:654701. doi: 10.3389/fimmu.2021.654701. eCollection 2021.
Systemic lupus erythematosus (SLE) is a chronic complex systemic autoimmune disease characterized by multiple autoantibodies and clinical manifestations, with the potential to affect nearly every organ. SLE treatments, including corticosteroids and immunosuppressive drugs, have greatly increased survival rates, but there is no curative therapy and SLE management is limited by drug complications and toxicities. There is an obvious clinical need for safe, effective SLE treatments. A promising treatment avenue is to restore immunological tolerance to reduce inflammatory clinical manifestations of SLE. Indeed, recent clinical trials of low-dose IL-2 supplementation in SLE patients showed that expansion of regulatory T cells (Treg cells) is associated with dramatic but transient improvement in SLE disease markers and clinical manifestations. However, the Treg cells that expanded were short-lived and unstable. Alternatively, antigen-specific tolerance (ASIT) approaches that establish long-lived immunological tolerance could be deployed in the context of SLE. In this review, we discuss the potential benefits and challenges of nanoparticle ASIT approaches to induce prolonged immunological tolerance in SLE.
系统性红斑狼疮(SLE)是一种慢性复杂的全身性自身免疫性疾病,其特征是存在多种自身抗体和临床表现,有可能影响几乎所有器官。SLE 的治疗方法,包括皮质类固醇和免疫抑制剂,大大提高了存活率,但目前尚无根治性疗法,且 SLE 的治疗受到药物并发症和毒性的限制。因此,临床上迫切需要安全有效的 SLE 治疗方法。一种很有前途的治疗途径是恢复免疫耐受,以减轻 SLE 的炎症临床表现。事实上,最近 SLE 患者使用低剂量白细胞介素 2(IL-2)补充治疗的临床试验表明,调节性 T 细胞(Treg 细胞)的扩增与 SLE 疾病标志物和临床表现的显著但短暂改善相关。然而,扩增的 Treg 细胞寿命短且不稳定。相反,在 SLE 背景下,可采用抗原特异性耐受(ASIT)方法来建立长期免疫耐受。在本文中,我们讨论了纳米颗粒 ASIT 方法在诱导 SLE 中产生长期免疫耐受方面的潜在益处和挑战。