Balancing Immunity: GSK-3's Divergent Roles in Dendritic Cell-Mediated T-Cell Priming and Memory Responses
Recommended Citation
Fu C, Ma T, Zhou L, Mi QS, and Jiang A. Balancing Immunity: GSK-3's Divergent Roles in Dendritic Cell-Mediated T-Cell Priming and Memory Responses. Int J Mol Sci 2025;26(13).
Document Type
Article
Publication Date
6-25-2025
Publication Title
Int J Mol Sci
Abstract
Glycogen synthase kinase-3 (GSK-3)-particularly the GSK-3β isoform-plays a pivotal role in regulating dendritic cell (DC) functions, including maturation, cytokine production, and antigen presentation. In immature DCs, GSK-3β is continuously active, and its inhibition has been shown to enhance DC maturation and function. As a key upstream kinase of β-catenin, GSK-3 inhibition activates β-catenin in both human and murine DCs-a pathway traditionally linked to its immunomodulatory effects. However, our recent findings challenge this paradigm by uncovering β-catenin-independent, dual roles of GSK-3β in DCs. Our study reveals that while GSK-3β enhances DC-mediated cross-priming of CD8 T cells, it concurrently impairs the generation of memory CD8 T cells. These findings have significant implications for vaccine development and cancer immunotherapy, where both effective T-cell priming and durable memory responses are critical. This mini-review provides an in-depth analysis of mechanistic insights into GSK-3β's paradoxical functions and discusses potential strategies to fine-tune GSK-3 activity for optimized immunotherapeutic outcomes.
Medical Subject Headings
Dendritic Cells; Humans; Animals; Immunologic Memory; Glycogen Synthase Kinase 3 beta; Glycogen Synthase Kinase 3; CD8-Positive T-Lymphocytes; T-Lymphocytes; Lymphocyte Activation; Antigen Presentation; beta Catenin
PubMed ID
40649856
Volume
26
Issue
13
