Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Glassman, Caleb R. | |
dc.contributor.author | Su, Leon | |
dc.contributor.author | Majri-Morrison, Sonia S. | |
dc.contributor.author | Winkelmann, Hauke | |
dc.contributor.author | Mo, Fei | |
dc.contributor.author | Li, Peng | |
dc.contributor.author | Perez-Cruz, Magdiel | |
dc.contributor.author | Ho, Peggy P. | |
dc.contributor.author | Koliesnik, Ievgen | |
dc.contributor.author | Nagy, Nadine | |
dc.contributor.author | Hnizdilova, Tereza | |
dc.contributor.author | Picton, Lora K. | |
dc.contributor.author | Kovar, Marek | |
dc.contributor.author | Bollyky, Paul | |
dc.contributor.author | Steinman, Lawrence | |
dc.contributor.author | Meyer, Everett | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Leonard, Warren J. | |
dc.contributor.author | Garcia, K. Christopher | |
dc.date.accessioned | 2021-12-23T16:21:49Z | - |
dc.date.available | 2021-12-23T16:21:49Z | - |
dc.date.issued | 2021 | |
dc.identifier.issn | 2050084X | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14030 | - |
dc.description.abstract | 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. | |
dc.description.sponsorship | National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R37-AI051321 K, 18-12973S, DGE-1656518]; National Institute of Allergy and Infectious Diseases R37-AI051321 K Christopher Garcia; Czech Science Foundation 18-12973S Marek Kovar; National Science Foundation DGE-1656518 Caleb R Glassman; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. | |
dc.language.iso | en | |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | |
dc.relation.ispartof | ELIFE | |
dc.subject | ALPHA-CHAIN | |
dc.subject | AUTOIMMUNITY | |
dc.subject | BETA-CHAIN | |
dc.subject | Biology | |
dc.subject | EXPRESSION | |
dc.subject | GAMMA-CHAIN | |
dc.subject | GENE | |
dc.subject | IL-2 RECEPTOR | |
dc.subject | Life Sciences & Biomedicine - Other Topics | |
dc.subject | MICE | |
dc.subject | MOLECULAR-CLONING | |
dc.subject | PROLIFERATION | |
dc.title | Calibration of cell-intrinsic interleukin-2 response thresholds guides design of a regulatory T cell biased agonist | |
dc.type | journal article | |
dc.identifier.doi | 10.7554/eLife.65777 | |
dc.identifier.isi | ISI:000653615000001 | |
dc.description.volume | 10 | |
dc.contributor.orcid | 0000-0002-3342-7989 | |
dc.contributor.orcid | 0000-0001-7654-9997 | |
dc.contributor.orcid | 0000-0002-8601-2568 | |
dc.contributor.orcid | 0000-0003-1215-2100 | |
dc.contributor.orcid | 0000-0003-3688-6854 | |
dc.publisher.place | SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND | |
dcterms.isPartOf.abbreviation | eLife | |
dcterms.oaStatus | gold, Green Published | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
Seitenaufrufe
2
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 15.05.2024