Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, Centre de Recherche du CHUS, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.
Int J Mol Sci. 2022 Apr 28;23(9):4885. doi: 10.3390/ijms23094885.
Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells through a process that is primarily mediated by T cells. Emerging evidence suggests that dendritic cells (DCs) play a crucial role in initiating and developing this debilitating disease. DCs are professional antigen-presenting cells with the ability to integrate signals arising from tissue infection or injury that present processed antigens from these sites to naïve T cells in secondary lymphoid organs, thereby triggering naïve T cells to differentiate and modulate adaptive immune responses. Recent advancements in our knowledge of the various subsets of DCs and their cellular structures and methods of orchestration over time have resulted in a better understanding of how the T cell response is shaped. DCs employ various arsenal to maintain their tolerance, including the induction of effector T cell deletion or unresponsiveness and the generation and expansion of regulatory T cell populations. Therapies that suppress the immunogenic effects of dendritic cells by blocking T cell costimulatory pathways and proinflammatory cytokine production are currently being sought. Moreover, new strategies are being developed that can regulate DC differentiation and development and harness the tolerogenic capacity of these cells. Here, in this report, we focus on recent advances in the field of DC immunology and evaluate the prospects of DC-based therapeutic strategies to treat T1D.
1 型糖尿病(T1D)是由 T 细胞主要介导的过程导致胰腺β细胞破坏引起的。新出现的证据表明,树突状细胞(DCs)在引发和发展这种使人衰弱的疾病方面起着至关重要的作用。DC 是具有整合来自组织感染或损伤的信号的能力的专业抗原呈递细胞,这些信号呈现来自这些部位的加工抗原,将其呈递给次级淋巴器官中的幼稚 T 细胞,从而触发幼稚 T 细胞分化并调节适应性免疫反应。我们对 DC 及其细胞结构和时间协调方法的各种亚群的认识的最新进展,使我们更好地理解了 T 细胞反应是如何形成的。DC 采用各种手段来维持其耐受性,包括诱导效应 T 细胞的缺失或无反应性,以及调节性 T 细胞群体的产生和扩增。目前正在寻找通过阻断 T 细胞共刺激途径和促炎细胞因子产生来抑制树突状细胞免疫原性的疗法。此外,正在开发新的策略来调节 DC 的分化和发育,并利用这些细胞的耐受性。在这里,我们重点介绍 DC 免疫学领域的最新进展,并评估基于 DC 的治疗策略治疗 T1D 的前景。
Int J Mol Sci. 2022-4-28
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