Single cell suppression profiling of human regulatory T cells
Abstract Regulatory T cells (Treg) play an important role in regulating immune homeostasis in health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide an accurate picture of a physiologically relevant response. To overc...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55746-1 |
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| author | Jonas Nørskov Søndergaard Janyerkye Tulyeu David Priest Shimon Sakaguchi James B. Wing |
| author_facet | Jonas Nørskov Søndergaard Janyerkye Tulyeu David Priest Shimon Sakaguchi James B. Wing |
| author_sort | Jonas Nørskov Søndergaard |
| collection | DOAJ |
| description | Abstract Regulatory T cells (Treg) play an important role in regulating immune homeostasis in health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide an accurate picture of a physiologically relevant response. To overcome this limitation, we here develop ‘single cell suppression profiling of human Tregs’ (scSPOT). scSPOT uses a 52-marker CyTOF panel, a cell division detection algorithm, and a whole PBMC system to assess the effect of Tregs on all other cell types simultaneously. In this head-to-head comparison, we find Tregs having the clearest suppressive effects on effector memory CD8 T cells through partial division arrest, cell cycle inhibition, and effector molecule downregulation. Additionally, scSPOT identifies a Treg phenotypic split previously observed in viral infection and propose modes of action by the FDA-approved drugs Ipilimumab and Tazemetostat. scSPOT is thus scalable, robust, widely applicable, and may be used to better understand Treg immunobiology and screen for therapeutic compounds. |
| format | Article |
| id | doaj-art-a3bdc425365f46779ea3409103e75df0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a3bdc425365f46779ea3409103e75df02025-02-09T12:44:43ZengNature PortfolioNature Communications2041-17232025-02-0116111610.1038/s41467-024-55746-1Single cell suppression profiling of human regulatory T cellsJonas Nørskov Søndergaard0Janyerkye Tulyeu1David Priest2Shimon Sakaguchi3James B. Wing4Human Immunology Team, Center for Infectious Disease Education and Research (CiDER), Osaka UniversityHuman Immunology Team, Center for Infectious Disease Education and Research (CiDER), Osaka UniversityLaboratory of Human Single Cell Immunology, WPI-IFReC, Osaka UniversityLaboratory of Experimental Immunology, WPI-IFReC, Osaka UniversityHuman Immunology Team, Center for Infectious Disease Education and Research (CiDER), Osaka UniversityAbstract Regulatory T cells (Treg) play an important role in regulating immune homeostasis in health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide an accurate picture of a physiologically relevant response. To overcome this limitation, we here develop ‘single cell suppression profiling of human Tregs’ (scSPOT). scSPOT uses a 52-marker CyTOF panel, a cell division detection algorithm, and a whole PBMC system to assess the effect of Tregs on all other cell types simultaneously. In this head-to-head comparison, we find Tregs having the clearest suppressive effects on effector memory CD8 T cells through partial division arrest, cell cycle inhibition, and effector molecule downregulation. Additionally, scSPOT identifies a Treg phenotypic split previously observed in viral infection and propose modes of action by the FDA-approved drugs Ipilimumab and Tazemetostat. scSPOT is thus scalable, robust, widely applicable, and may be used to better understand Treg immunobiology and screen for therapeutic compounds.https://doi.org/10.1038/s41467-024-55746-1 |
| spellingShingle | Jonas Nørskov Søndergaard Janyerkye Tulyeu David Priest Shimon Sakaguchi James B. Wing Single cell suppression profiling of human regulatory T cells Nature Communications |
| title | Single cell suppression profiling of human regulatory T cells |
| title_full | Single cell suppression profiling of human regulatory T cells |
| title_fullStr | Single cell suppression profiling of human regulatory T cells |
| title_full_unstemmed | Single cell suppression profiling of human regulatory T cells |
| title_short | Single cell suppression profiling of human regulatory T cells |
| title_sort | single cell suppression profiling of human regulatory t cells |
| url | https://doi.org/10.1038/s41467-024-55746-1 |
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