Immunometabolism of Regulatory T Cells Enhanced by Lipid Nanoparticles
1Department of Medicine, Division of Hematology/ Oncology, Northwestern University, Chicago, IL, 2Comprehensive Transplant Center, Northwestern University, Chicago, IL, 3Northwestern University, Chicago, IL, 4Surgery, Northwestern Medicine, Chicago, IL, 5Department of Urology, Northwestern University, Chicago, IL
Meeting: 2022 American Transplant Congress
Abstract number: 1262
Keywords: Bioengineering, Gene expression, Lipids, T cells
Topic: Basic Science » Basic Science » 10 - Treg/Other Regulatory Cell/Tolerance
Session Information
Session Name: Treg/Other Regulatory Cell/Tolerance
Session Type: Poster Abstract
Date: Monday, June 6, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Human regulatory T cell (Treg) metabolism is highly dependent upon a number of factors, including cholesterol obtained from circulating lipoproteins. We have developed high-density lipoproteins-like nanoparticles (HDL NPs), which mimic mature, cholesterol-rich HDLs, with the aim of improving ex vivo Treg cell expansion and survival.
*Methods: HDL-like nanoparticles (HDL NPs) were templated using either a gold (Au) nanoparticle core or a soft organic tetrahedral core (oc), and mimic the size, shape and surface composition of mature, spherical HDLs. HDL NPs specifically target the high affinity HDL receptor scavenger receptor type B1 (SR-B1). Treg cells were polyclonally expanded in the presence of Au- or oc-HDL NPs, or controls [PBS, reconstituted HDL (rHDL)] and assayed for proliferation (by cell counts), survival (by flow cytometry), expression of Treg markers, SR-B1 and cholesterol biosynthesis genes (by RT-qPCR and flow cytometry), and total cellular cholesterol levels (by Amplex Red cholesterol assay).
*Results: Culture of Tregs with Au and oc HDL NPs did not affect the markers of Treg such as CD3, CD4, CD25 and FoxP3 expression compared to PBS control. However, Au- and oc-HDL NPs significantly increased SR-B1 expression during the first 7 days of treatment. Further, Au-HDL NP treatment of Treg cells increased expression of cholesterol biosynthesis genes during the first 7 days of treatment, including among others HMG Co-A synthase 1 (1.00 ± 0.16 for PBS vs. 1.36 ± 0.09 for Au-HDL NP treated) and 7-dehydrocholesterol reductase (1.00 ± 0.09 vs. 1.21 ± 0.07), which was not seen with oc-HDL NPs and rHDL. Total cellular cholesterol content was not altered with Au- or oc-HDL NP treatment over a treatment period of 21 days. Treg proliferation increased with Au- (1.97) and oc-HDL NP (1.11) treatment, as well as rHDL (1.63), compared to PBS control (1.00), while having no adverse effects on viability.
*Conclusions: These results demonstrate that targeting SR-B1 with HDL-like nanoparticles can alter the immunometabolic state of Treg cells and promote proliferation during ex vivo expansion.
To cite this abstract in AMA style:
Rink JS, Sambandam Y, He J, Mathew J, Leventhal JR, Thaxton CS. Immunometabolism of Regulatory T Cells Enhanced by Lipid Nanoparticles [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/immunometabolism-of-regulatory-t-cells-enhanced-by-lipid-nanoparticles/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress