In Vivo Accumulation of Regulatory T Cells Using Eliglustat‐Loaded Cryogels

Regulatory T cells are essential to maintain immune homeostasis and mitigate inflammatory and autoimmune conditions, however, their isolation and expansion is challenging. The utilization of a small molecule, eliglustat, is explored to promote regulatory T cell formation and to design an injectable biomaterial niche that allows direct in vivo T cell accumulation and regulatory phenotype induction.

Abstract

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.