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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 05, 2023 |
| Title |
Attenuated IL-2 muteins promote regulatory T cell adaptation of the effector phenotype and function in vivo via modified IL-2 responses |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins.
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| Overall design |
Four different IL-2 treatment conditions (PBS, WT IL-2, H16R, and 3x mutein) within 2 antibody treatment groups (isotype and MHC II blocking antibodies) were evaluated with 4 mice in each group, resulting in a total of 32 Treg samples. CD25- Tcons from two mice from each group were included for comparison.
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| Contributor(s) |
Ma S, So M, Ghelani A, Srivas R, Sahoo A, Hall R, Liu W, Wu H, Yu S, Lu S, Song E, Cariaga T, Soto M, Zhou H, Li C, Chaudhry A, Luo X, Sohn SJ |
| Citation(s) |
37809101 |
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| Submission date |
Oct 19, 2022 |
| Last update date |
Oct 18, 2023 |
| Contact name |
Shining Ma |
| E-mail(s) |
sma05@amgen.com
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| Organization name |
Amgen Inc.
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| Street address |
1120 Veterans Blvd
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| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
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| Samples (48)
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| GSM6659042 |
4_A1-4 Treg,Isotype,PBS |
| GSM6659043 |
5_A2-1 Treg,Isotype,WT |
| GSM6659044 |
6_A2-2 Treg,Isotype,WT |
| GSM6659045 |
7_A2-3 Treg,Isotype,WT |
| GSM6659046 |
8_A2-3 Treg,Isotype,WT |
| GSM6659047 |
9_A3-1 Treg,Isotype,IL2 (H16R) |
| GSM6659048 |
10_A3-2 Treg,Isotype,IL2 (H16R) |
| GSM6659049 |
11_A3-3 Treg,Isotype,IL2 (H16R) |
| GSM6659050 |
12_A3-4 Treg,Isotype,IL2 (H16R) |
| GSM6659051 |
13_A4-1 Treg,Isotype,IL2 (3x) |
| GSM6659052 |
14_A4-2 Treg,Isotype,IL2 (3x) |
| GSM6659053 |
15_A4-3 Treg,Isotype,IL2 (3x) |
| GSM6659054 |
16_A4-4 Treg,Isotype,IL2 (3x) |
| GSM6659055 |
17_B1-1 Treg,MHCII-Block,PBS |
| GSM6659056 |
18_B1-2 Treg,MHCII-Block,PBS |
| GSM6659057 |
19_B1-3 Treg,MHCII-Block,PBS |
| GSM6659058 |
20_B1-4 Treg,MHCII-Block,PBS |
| GSM6659059 |
21_B2-1 Treg,MHCII-Block,WT |
| GSM6659060 |
22_B2-2 Treg,MHCII-Block,WT |
| GSM6659061 |
23_B2-3 Treg,MHCII-Block,WT |
| GSM6659062 |
24_B2-4 Treg,MHCII-Block,WT |
| GSM6659063 |
25_B3-1 Treg,MHCII-Block,IL2 (H16R) |
| GSM6659064 |
26_B3-2 Treg,MHCII-Block,IL2 (H16R) |
| GSM6659065 |
27_B3-3 Treg,MHCII-Block,IL2 (H16R) |
| GSM6659066 |
28_B3-4 Treg,MHCII-Block,IL2 (H16R) |
| GSM6659067 |
29_B4-1 Treg,MHCII-Block,IL2 (3x) |
| GSM6659068 |
30_B4-2 Treg,MHCII-Block,IL2 (3x) |
| GSM6659069 |
31_B4-3 Treg,MHCII-Block,IL2 (3x) |
| GSM6659070 |
32_B4-4 Treg,MHCII-Block,IL2 (3x) |
| GSM6659071 |
33_CD25- A1-1,Isotype,PBS |
| GSM6659072 |
34_CD25- A1-2,Isotype,PBS |
| GSM6659073 |
35_CD25- A2-1,Isotype,WT |
| GSM6659074 |
36_CD25- A2-2,Isotype,WT |
| GSM6659075 |
37_CD25- A3-1,Isotype,IL2 (H16R) |
| GSM6659076 |
38_CD25- A3-2,Isotype,IL2 (H16R) |
| GSM6659077 |
39_CD25- A4-1,Isotype,IL2 (3x) |
| GSM6659078 |
40_CD25- A4-2,Isotype,IL2 (3x) |
| GSM6659079 |
41_CD25- B1-1,MHCII-Block,PBS |
| GSM6659080 |
42_CD25- B1-2,MHCII-Block,PBS |
| GSM6659081 |
43_CD25- B2-1,MHCII-Block,WT |
| GSM6659082 |
44_CD25- B2-2,MHCII-Block,WT |
| GSM6659083 |
45_ CD25- B3-1,MHCII-Block,IL2 (H16R) |
| GSM6659084 |
46_CD25- B3-2,MHCII-Block,IL2 (H16R) |
| GSM6659085 |
47_ CD25- B4-1,MHCII-Block,IL2 (3x) |
| GSM6659086 |
48_CD25- B4-2,MHCII-Block,IL2 (3x) |
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| Relations |
| BioProject |
PRJNA892130 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216130_Treg_Isotype_DEG_ByDESeq2.csv.gz |
2.7 Mb |
(ftp)(http) |
CSV |
| GSE216130_Treg_MHC_II_DEG_ByDESeq2.csv.gz |
2.7 Mb |
(ftp)(http) |
CSV |
| GSE216130_Treg_sample_treatment_comparison_DEG_ByDESeq2.csv.gz |
1.9 Mb |
(ftp)(http) |
CSV |
| GSE216130_gene_Counts_Matrix.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
| GSE216130_gene_FPKM_Matrix.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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