CEMatrix-Bound Hyaluronan Molecular Weight as A Regulator of Dendritic Cell Immune Potency.

Hyaluronic acid (HA) is a glycosaminoglycan in the extracellular matrix with immunoregulatory properties depending on its molecular weight (MW). However, the impact of matrix-bound HA on dendritic cells (DCs) remains unclear due to varying distribution of HA MW under different physiological conditions. To investigate DCs in defined biosystems, we used 3D collagen matrices modified with HA of specific MW with similar microstructure and HA levels. We found that HA MW influenced cytokine binding to matrix, suggesting modulation of cytokine availability by the different MWs of HA. Our studies on DC immune potency revealed that low MW HA (LMW-HA;8-15 kDa) enhanced immature DC differentiation and antigen uptake, while medium (MMW-HA;500-750 kDa) and high MW HA (HMW-HA;1250-1500 kDa) increased cytokine secretion in mature DCs. The effect on DC phenotype and cytokine secretion by different MWs of HA was independent of CD44. However, blocking the CD44 receptor revealed its potential role in regulating acute inflammation through increased secretion of CCL2, CXCL8, and IL-6. Additionally, MMW- and HMW-HA matrices reduced migratory capacity of DCs, dependent on CD44. Overall, our findings provide insights into MW-dependent effects of matrix-bound HA on DCs, opening avenues for the design of DC-modulating materials to enhance DC-based therapy. This article is protected by copyright. All rights reserved.