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GEO help: Mouse over screen elements for information. |
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Status |
Public on Nov 01, 2012 |
Title |
Mechanistic and structural insight into the functional dichotomy between interleukin-2 and interleukin-15 |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Interleukin-15 (IL-15) and IL-2 possess distinct immunological functions despite both signaling through IL-2Rβ and the common cytokine receptor γ-chain, γc, We find that in the IL-15/IL-15Rα/IL-2Rβ/γc quaternary complex structure, IL-15 heterodimerizes IL-2Rβ and γc identically to the IL-2/IL-2Rα/IL-2Rβ/γc complex, despite differing receptor-binding chemistries. IL-15Rα dramatically increases the affinity of IL-15 for IL-2Rβ, and this allostery is required for IL-15 trans-signaling versus IL-2 cis-signaling. Consistent with the identical IL-2Rβ/γc dimer geometry, IL-2 and IL-15 exhibited similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induce similar signals, and the cytokine-specificity of IL-2Rα versus IL-15Rα determines cellular responsiveness. These results provide important new insights for specific development of IL-15- versus IL-2-based immunotherapeutics.
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Overall design |
RNA-Seq is conducted in mouse CD8+ T cells, not treated or treated with IL2 or IL15 for indicated concentrations (1nM or 500nM) and times (4hr or 24hr).
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Contributor(s) |
Ring AM, Lin J, Feng D, Mitra S, Rickert M, Bowman GR, Pande V, Li P, Moraga I, Spolski R, Özkan E, Leonard WJ, Garcia K |
Citation(s) |
23104097 |
Submission date |
Aug 23, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Peng Li |
E-mail(s) |
peng.li@nih.gov
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Organization name |
NIH
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Department |
NHLBI
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Lab |
LMI
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Street address |
9000 Rockville Pike
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (9)
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Relations |
BioProject |
PRJNA173649 |
SRA |
SRP015113 |
Supplementary file |
Size |
Download |
File type/resource |
GSE40350_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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