Yi Young-Su
Department of Life Sciences, Kyonggi University, Suwon 16227, Republic of Korea.
Int J Mol Sci. 2025 Sep 12;26(18):8893. doi: 10.3390/ijms26188893.
Inflammation is an innate immune system protecting the body from infection and injury. This process proceeds through two distinct stages: a priming phase, characterized by transcriptional activation, and a triggering phase, in which inflammasomes, cytosolic multiprotein complexes, are activated to initiate inflammatory signaling cascades. Canonical inflammasomes, the first to be identified, have been extensively implicated in the pathogenesis of diverse inflammatory disorders. In contrast, noncanonical inflammasomes have only recently been characterized, and their precise contributions to immune regulation and disease development remain incompletely defined. Diabetes mellitus (DM), simply diabetes, represents a heterogeneous group of metabolic disorders marked by chronic hyperglycemia and is associated with a broad spectrum of complications. The involvement of canonical inflammasomes in DM and its complications has been well demonstrated. More recently, however, accumulating evidence has uncovered crucial roles for noncanonical inflammasomes in the pathogenesis of DM and related complications This review comprehensively discusses current advances in understanding the regulatory functions of murine caspase-11 and human caspase-4/5 noncanonical inflammasomes in the pathogenesis of DM and diabetes-associated complications, highlighting their potential as novel therapeutic targets.
炎症是一种先天性免疫系统，可保护身体免受感染和损伤。这个过程通过两个不同阶段进行：一个启动阶段，其特征是转录激活；以及一个触发阶段，在此阶段炎性小体（胞质多蛋白复合物）被激活以启动炎症信号级联反应。经典炎性小体是最早被鉴定出来的，已被广泛认为与多种炎症性疾病的发病机制有关。相比之下，非经典炎性小体直到最近才被描述，它们对免疫调节和疾病发展的确切作用仍未完全明确。糖尿病（DM），简称糖尿病，是一组以慢性高血糖为特征的异质性代谢紊乱疾病，并伴有广泛的并发症。经典炎性小体在糖尿病及其并发症中的作用已得到充分证实。然而，最近越来越多的证据揭示了非经典炎性小体在糖尿病及其相关并发症发病机制中的关键作用。本综述全面讨论了在理解小鼠半胱天冬酶 -11和人类半胱天冬酶 -4/5非经典炎性小体在糖尿病及其相关并发症发病机制中的调节功能方面的当前进展，强调了它们作为新型治疗靶点的潜力。
