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

Area of Science:

• Immunology
• Biomaterials Science
• Pharmacology

Background:

• Regulatory T cells (Tregs) are crucial for immune homeostasis and are investigated for treating inflammatory and autoimmune diseases.
• Current Treg-based therapies often require ex vivo isolation and adoptive transfer, which can be complex and costly.

Purpose of the Study:

• To develop a biomaterial-based strategy to enhance the local accumulation of Tregs in vivo.
• To investigate the potential of eliglustat, a known drug, in promoting Treg function and accumulation within a biomaterial scaffold.

Main Methods:

• Fabrication of click-crosslinked alginate-collagen cryogels for sustained release of chemokines (CXCL10/CXCL11).
• In vitro assessment of eliglustat's effect on Treg promotion from CD4+ T cells.
• In vivo evaluation of eliglustat-loaded cryogels for their ability to enrich Tregs at the injection site.

Main Results:

• Eliglustat was shown to promote Tregs from both naïve and activated CD4+ T cells in vitro.
• Cryogels released chemokines, attracting effector and memory T cells to the scaffold.
• Loading eliglustat into the cryogels significantly increased the in vivo accumulation of Tregs at the local site.

Conclusions:

• Eliglustat-loaded cryogels represent a promising biomaterial strategy for boosting local Treg populations in vivo.
• This approach bypasses the need for ex vivo Treg isolation and adoptive transfer, offering a simpler therapeutic method.
• The developed biomaterial holds potential for targeted treatment of inflammatory and autoimmune conditions.