Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo
Name
elife-58463-v3.pdf
Description
Published version
Size
3.97 MB
Format
Adobe PDF
Checksum (MD5)
be27e1cae27ad5d4a4d7dbab403d5e56
Author(s)
Fernandes, Ricardo A
Li, Chaoran
Wang, Gang
Yang, Xinbo
Savvides, Christina S
Glassman, Caleb R
Dong, Shen
Luxenberg, Eric
Sibener, Leah V
Birnbaum, Michael E
Date Issued
2020
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
© Fernandes et al. T regulatory (Treg) cells play vital roles in modulating immunity and tissue homeostasis. Their actions depend on TCR recognition of peptide-MHC molecules; yet the degree of peptide specificity of Treg-cell function, and whether Treg ligands can be used to manipulate Treg cell biology are unknown. Here, we developed an Ab-peptide library that enabled unbiased screening of peptides recognized by a bona fide murine Treg cell clone isolated from the visceral adipose tissue (VAT), and identified surrogate agonist peptides, with differing affinities and signaling potencies. The VAT-Treg cells expanded in vivo by one of the surrogate agonists preserved the typical VAT-Treg transcriptional programs. Immunization with this surrogate, especially when coupled with blockade of TNFα signaling, expanded VAT-Treg cells, resulting in protection from inflammation and improved metabolic indices, including promotion of insulin sensitivity. These studies suggest that antigen-specific targeting of VAT-localized Treg cells could eventually be a strategy for improving metabolic disease.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/ELIFE.58463
