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| Status |
Public on Jan 15, 2021 |
| Title |
Efficient IL-2R signaling differentially affects stability, function, and composition of the regulatory T cell pool |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Signaling via the interleukin 2 receptor (IL-2R) is a requisite for Treg cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function during both resting and inflammatory conditions. Here, we characterized a spontaneous mouse mutant endowed with a hypomorphic Tyr129His variant of CD25, the a chain of the IL 2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under non-inflammatory conditions Cd25-Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune diseases. In contrast, Cd25-Y129H Treg cells failed to efficiently induce immune suppression and lost linage commitment in a T cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with maintenance, heterogeneity and suppressive function of the regulatory T cell pool.
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| Overall design |
CD4+Foxp3+ Treg cells were sorted from spleens of WT or CD25-Y129H Foxp3-GFP mice by flow cytometry and subjected to single-cell RNA sequencing (10x genomics).
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| Contributor(s) |
Permanyer M, Bošnjak B, Förster R |
| Citation(s) |
33408345 |
| Submission date |
Nov 12, 2020 |
| Last update date |
Jan 17, 2021 |
| Contact name |
Berislav Bosnjak |
| E-mail(s) |
bosnjak.berislav@mh-hannover.de
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| Phone |
+495115329731
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| Organization name |
Hannover Medical School
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| Department |
Institute of Immunology
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| Street address |
Carl-Neuberg Straße 1
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| City |
Hannover |
| ZIP/Postal code |
30625 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA677933 |
| SRA |
SRP292332 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161345_RAW.tar |
99.2 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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