Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo

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. H...

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Hlavní autoři: Ricardo A Fernandes, Chaoran Li, Gang Wang, Xinbo Yang, Christina S Savvides, Caleb R Glassman, Shen Dong, Eric Luxenberg, Leah V Sibener, Michael E Birnbaum, Christophe Benoist, Diane Mathis, K Christopher Garcia
Médium: Článek
Jazyk:English
Vydáno: eLife Sciences Publications Ltd 2020-08-01
Edice:eLife
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On-line přístup:https://elifesciences.org/articles/58463
Popis
Shrnutí: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.
ISSN:2050-084X