Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F21%3A00543231" target="_blank" >RIV/61388971:_____/21:00543231 - isvavai.cz</a>
Result on the web
<a href="https://elifesciences.org/articles/65777" target="_blank" >https://elifesciences.org/articles/65777</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.7554/eLife.65777" target="_blank" >10.7554/eLife.65777</a>

Result language
angličtina
Original language name
Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist
Original language description
Interleukin-2 is a pleiotropic cytokine that mediates both pro- and anti-inflammatory functions. Immune cells naturally differ in their sensitivity to IL-2 due to cell type and activation state-dependent expression of receptors and signaling pathway components. To probe differences in IL-2 signaling across cell types, we used structure-based design to create and profile a series of IL-2 variants with the capacity to titrate maximum signal strength in fine increments. One of these partial agonists, IL-2-REH, specifically expanded Foxp3+ regulatory T cells with reduced activity on CD8+ T cells due to cell type-intrinsic differences in IL-2 signaling. IL-2-REH elicited cell typedependent differences in gene expression and provided mixed therapeutic results: showing benefit in the in vivo mouse dextran sulfate sodium (DSS) model of colitis, but no therapeutic efficacy in a transfer colitis model. Our findings show that cytokine partial agonists can be used to calibrate intrinsic differences in response thresholds across responding cell types to narrow pleiotropic actions, which may be generalizable to other cytokine and growth factor systems.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology

Project
<a href="/en/project/GA18-12973S" target="_blank" >GA18-12973S: IL-2 complexed with muteins of JES6-1 mAb having different affinity to IL-2: finding variant with most selective stimulation of Treg cells in vivo</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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