Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets
Summary: Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTr...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224024738 |
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| author | Acacia N. Shouse Alejandro V. Villarino Thomas R. Malek |
| author_facet | Acacia N. Shouse Alejandro V. Villarino Thomas R. Malek |
| author_sort | Acacia N. Shouse |
| collection | DOAJ |
| description | Summary: Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs). Unexpectedly, ablation of IL-2R signaling in cTregs resulted in increased proliferation, expression of eTreg genes, and enhanced capacity to develop into eTregs. Thus, IL-2R signaling normally acts as a checkpoint to maintain cTreg homeostasis while restraining their development into eTregs. Loss of IL-2R signaling also alters the distribution of eTreg subsets, with increased IFNγR1+ eTregs and CXCR5+ PD-1+ T follicular regulatory (TFR) cells but decreased intestinal RORγt+ TR17 cells. These changes lower eTreg suppressive function supporting expansion of IFNγ-secreting T effector cells. Thus, IL-2R signaling also safeguards Treg function and licenses differentiation of specialized eTregs. |
| format | Article |
| id | doaj-art-93a01a499b8c42a39a16ec4a82a2e7bd |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-93a01a499b8c42a39a16ec4a82a2e7bd2024-12-22T05:28:42ZengElsevieriScience2589-00422024-12-012712111248Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsetsAcacia N. Shouse0Alejandro V. Villarino1Thomas R. Malek2Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Corresponding authorSummary: Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we show that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of circulating Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs). Unexpectedly, ablation of IL-2R signaling in cTregs resulted in increased proliferation, expression of eTreg genes, and enhanced capacity to develop into eTregs. Thus, IL-2R signaling normally acts as a checkpoint to maintain cTreg homeostasis while restraining their development into eTregs. Loss of IL-2R signaling also alters the distribution of eTreg subsets, with increased IFNγR1+ eTregs and CXCR5+ PD-1+ T follicular regulatory (TFR) cells but decreased intestinal RORγt+ TR17 cells. These changes lower eTreg suppressive function supporting expansion of IFNγ-secreting T effector cells. Thus, IL-2R signaling also safeguards Treg function and licenses differentiation of specialized eTregs.http://www.sciencedirect.com/science/article/pii/S2589004224024738Biological sciencesImmune responseImmunologyNatural sciences |
| spellingShingle | Acacia N. Shouse Alejandro V. Villarino Thomas R. Malek Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets iScience Biological sciences Immune response Immunology Natural sciences |
| title | Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets |
| title_full | Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets |
| title_fullStr | Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets |
| title_full_unstemmed | Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets |
| title_short | Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets |
| title_sort | interleukin 2 receptor signaling acts as a checkpoint that influences the distribution of regulatory t cell subsets |
| topic | Biological sciences Immune response Immunology Natural sciences |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224024738 |
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