Group Immune Tolerance in Type 1 Diabetes, Helmholtz Diabetes Center at Helmholtz Zentrum München, Institute of Diabetes Research, Munich, Germany.
Deutsches Zentrum für Diabetesforschung (DZD), Neuherberg, Germany.
Front Immunol. 2021 Jul 22;12:712870. doi: 10.3389/fimmu.2021.712870. eCollection 2021.
Regulatory T cells (Tregs) are key mediators of peripheral self-tolerance and alterations in their frequencies, stability, and function have been linked to autoimmunity. The antigen-specific induction of Tregs is a long-envisioned goal for the treatment of autoimmune diseases given reduced side effects compared to general immunosuppressive therapies. However, the translation of antigen-specific Treg inducing therapies for the treatment or prevention of autoimmune diseases into the clinic remains challenging. In this mini review, we will discuss promising results for antigen-specific Treg therapies in allergy and specific challenges for such therapies in autoimmune diseases, with a focus on type 1 diabetes (T1D). We will furthermore discuss opportunities for antigen-specific Treg therapies in T1D, including combinatorial strategies and tissue-specific Treg targeting. Specifically, we will highlight recent advances in miRNA-targeting as a means to foster Tregs in autoimmunity. Additionally, we will discuss advances and perspectives of computational strategies for the detailed analysis of tissue-specific Tregs on the single-cell level.
调节性 T 细胞（Tregs）是外周自身耐受的关键介质，其频率、稳定性和功能的改变与自身免疫有关。与一般的免疫抑制疗法相比，抗原特异性诱导 Tregs 的产生是治疗自身免疫性疾病的一个长期目标，因为其副作用较小。然而，将针对自身免疫性疾病的抗原特异性 Treg 诱导治疗转化为临床应用仍然具有挑战性。在这篇迷你综述中，我们将讨论在过敏症中抗原特异性 Treg 治疗的有希望的结果，以及此类治疗在自身免疫性疾病中存在的特殊挑战，重点是 1 型糖尿病（T1D）。我们还将讨论 T1D 中抗原特异性 Treg 治疗的机会，包括组合策略和组织特异性 Treg 靶向。具体来说，我们将强调 miRNA 靶向作为在自身免疫中促进 Tregs 的一种手段的最新进展。此外，我们还将讨论计算策略在单细胞水平上对组织特异性 Tregs 进行详细分析的进展和前景。
