In Vivo Accumulation of Regulatory T Cells Using Eliglustat-Loaded Cryogels.

Regulatory T cells (T(regs)) maintain immune homeostasis and their adoptive transfer is being widely explored to mitigate inflammatory and autoimmune conditions. Here a biomaterial is developed to accumulate T(regs) at a specific anatomic location to bypass the need for ex vivo T(reg) isolation and adoptive transfer. It is first shown that eliglustat, an FDA-approved inhibitor of UDP-glucose ceramide glucosyltransferase, promotes T(regs) from both naïve and activated CD4(+) T cells in vitro. Click-crosslinked cryogels fabricated from alginate and collagen allow for a sustained release of CXCL10 or CXCL11, and when injected in subcutaneous tissues led to the enrichment of effector and memory T cells to the scaffolds. Loading eliglustat into these cryogels significantly enhances the local accumulation of T(regs) in vivo. These findings demonstrate that eliglustat-loaded cryogels offer a simple yet effective biomaterial strategy to boost T(reg) directly in vivo, potentially providing a targeted method to treat various inflammatory and autoimmune diseases.