Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Permanyer, MarcBošnjak, Berislav
Glage, Silke
Friedrichsen, Michaela
Floess, Stefan
Huehn, Jochen

Patzer, Gwendolyn E
Odak, Ivan
Eckert, Nadine
Zargari, Razieh
Ospina-Quintero, Laura
Georgiev, Hristo
Förster, Reinhold
Issue Date
2021-01-06
Metadata
Show full item recordAbstract
Signaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (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 in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25Y129H Treg cells failed to efficiently induce immune suppression and lost lineage 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 the maintenance, heterogeneity, and suppressive function of the Treg cell pool.Citation
Cell Mol Immunol. 2021 Feb;18(2):398-414. doi: 10.1038/s41423-020-00599-z. Epub 2021 JanAffiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
Springer NatureJournal
Cellular & molecular immunologyPubMed ID
33408345Type
ArticleLanguage
enEISSN
2042-0226ae974a485f413a2113503eed53cd6c53
10.1038/s41423-020-00599-z
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
Related articles
- Acute Lipopolysaccharide-Induced Inflammation Lowers IL-2R Signaling and the Proliferative Potential of Regulatory T Cells.
- Authors: Hsiung S, Moro A, Ban Y, Chen X, Savio AS, Hernandez R, Malek TR
- Issue date: 2020 Dec 17
- A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells.
- Authors: Bayer AL, Lee JY, de la Barrera A, Surh CD, Malek TR
- Issue date: 2008 Jul 1
- Interleukin-7 optimizes FOXP3+CD4+ regulatory T cells reactivity to interleukin-2 by modulating CD25 expression.
- Authors: Simonetta F, Gestermann N, Bloquet S, Bourgeois C
- Issue date: 2014
- IL-2Rbeta links IL-2R signaling with Foxp3 expression.
- Authors: Soper DM, Kasprowicz DJ, Ziegler SF
- Issue date: 2007 Jul
- IL-2R signaling is essential for functional maturation of regulatory T cells during thymic development.
- Authors: Cheng G, Yu A, Dee MJ, Malek TR
- Issue date: 2013 Feb 15