Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes.
Fangfang Jin, Wei-Dong Wu, Xuan Yang et al.· International Journal of Mol...· 0 citations
AD is a complex neurodegenerative disorder characterized by chronic neuroinflammation. Microglia, the brain's resident immune cells, centrally regulate AD pathophysiology. Recent studies have highlighted microglial mitophagy as an important interface linking mitochondrial quality control to innate immune responses.Intact mitophagy facilitates the timely clearance of damaged mitochondria, thereby limiting the release of mitochondrial DAMPs (e.g., mtDNA and mtROS) and helping restrain aberrant activation of the cGAS-STING pathway and the NLRP3 inflammasome.In the AD pathological milieu, however, factors including Aβ deposition, tau pathology, and genetic risk variants such as TREM2 and APOE4 disrupt mitophagy at multiple levels-from initiation and recognition to lysosomal degradation. This review systematically summarizes the molecular regulatory network of microglial mitophagy, with a particular focus on the mechanisms by which AD-associated pathological factors impair this process. We further discuss potential mechanisms through which mitophagic dysfunction may contribute to the amplification of neuroinflammation, including the release of mitochondrial DAMPs, the reprogramming of TBK1 signaling, and intercellular interactions. Finally, we outline current therapeutic strategies aimed at restoring mitophagy and discuss their potential to modulate neuroinflammatory responses and AD-related pathological processes, while highlighting the challenges and future directions in this emerging field.
Mingyue Zou, Tengyu Zhao, Wei-Dong Wu et al.· Journal of Neuroinflammation· 0 citations
