Extracellular Fluid Viscosity Regulates the Immune Functions of Bone Marrow-Derived Immature Dendritic Cells

The extracellular microenvironment shapes dendritic cell function through its mechanical properties, yet the role of extracellular fluid (ECF) viscosity remains unknown. Here, a medium with tunable ECF viscosity was constructed by using a hyaluronic acid/gelatin supramolecular polymer. The results demonstrate that bone marrow-derived dendritic cells (BMDCs) cultured in 15 cP ECF exhibit increased expression of costimulatory molecules and pro-inflammatory cytokines, alongside decreased secretion of anti-inflammatory cytokines. Moreover, exposure to high-viscosity conditions impaired the BMDCs' motility and FITC-dextran endocytic capacity. Elevated ECF viscosity also promoted the differentiation of Th₁ and Th₁₇ cell subsets while suppressing the differentiation of CD4⁺ T cells into regulatory T cells. RNA seq indicates that the BMDCs' response to ECF viscosity may be mediated through the PI3K-Akt and NOD-like receptor signaling pathways. Collectively, these findings reveal a mechano-immunological axis wherein ECF viscosity dynamically regulates DC activation and subsequent T-cell priming, highlighting the interaction between the physical microenvironment and adaptive immunity.