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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eLife Sciences Publications Ltd
2020-08-01
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| 丛编: | eLife |
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| 在线阅读: | https://elifesciences.org/articles/58463 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ricardo A Fernandes |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:53:56Z |
| format | Article |
| id | doaj.art-901b336084904a38bd5004c2630ed0ff |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:53:56Z |
| publishDate | 2020-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-901b336084904a38bd5004c2630ed0ff2022-12-22T02:05:06ZengeLife Sciences Publications LtdeLife2050-084X2020-08-01910.7554/eLife.58463Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivoRicardo A Fernandes0https://orcid.org/0000-0001-5343-3334Chaoran Li1Gang Wang2Xinbo Yang3Christina S Savvides4Caleb R Glassman5Shen Dong6Eric Luxenberg7Leah V Sibener8Michael E Birnbaum9Christophe Benoist10Diane Mathis11K Christopher Garcia12https://orcid.org/0000-0001-9273-0278Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartment of Immunology, Harvard Medical School; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, United StatesDepartment of Immunology, Harvard Medical School; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartment of Electrical Engineering, Stanford University School of Engineering, Stanford, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United StatesDepartment of Immunology, Harvard Medical School; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, United StatesDepartment of Immunology, Harvard Medical School; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, United StatesDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United States; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United StatesT 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.https://elifesciences.org/articles/58463inflammationTreg cellsadipose tissuesurrogate antigens |
| spellingShingle | 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 Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo eLife inflammation Treg cells adipose tissue surrogate antigens |
| title | Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo |
| title_full | Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo |
| title_fullStr | Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo |
| title_full_unstemmed | Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo |
| title_short | Discovery of surrogate agonists for visceral fat Treg cells that modulate metabolic indices in vivo |
| title_sort | discovery of surrogate agonists for visceral fat treg cells that modulate metabolic indices in vivo |
| topic | inflammation Treg cells adipose tissue surrogate antigens |
| url | https://elifesciences.org/articles/58463 |
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