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Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool.

Permanyer, Marc
; 
Bošnjak, Berislav
; 
Glage, Silke
; 
Friedrichsen, Michaela
; 
Floess, Stefan
; ; 
Patzer, Gwendolyn E
; 
Odak, Ivan
; 
Eckert, Nadine
; 
Zargari, Razieh
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Issue Date
2021-01-06
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Abstract
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 Jan
Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Publisher
Springer Nature
Journal
Cellular & molecular immunology
URI
http://hdl.handle.net/10033/622748
DOI
10.1038/s41423-020-00599-z
PubMed ID
33408345
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Article
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en
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2042-0226
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Attribution-NonCommercial-ShareAlike 4.0 International
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publications of the research group experimentelle Immunologie (EXIM)