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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 07, 2023 |
| Title |
IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE. However, the underlying mechanism by which IL-6 may prevent the development of Th2-driven diseases remains unknown. Using a model of house-dust-mite (HDM)-induced Th2 differentiation and allergic airway inflammation, we show here that IL-6 signaling in allergen-specific T cells was required to prevent Th2 development and subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. Importantly, we found that IL-6 turned off IL-2 signaling during early T cell activation and thus inhibited Th2 cell priming. Mechanistically, we found that IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of suppressor of cytokine signaling 3 (SOCS3). Therapeutically, this mechanism can be mimicked by JAK1 inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.
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| Overall design |
WT and Il6-/- mice were transferred with OTII TCR-transgenic CD4+ T cells and intranasally sensitized with 100 micrograms HDM extract (endotoxin content ~250 EU/mg) + 5 micrograms of LPS-free EndoFit ovalbumin. On day 3 and day 5, OTII cells were sorted from mediastinal lymph nodes and RNA-seq was performed (three replicates). The manuscript time references start at day 0 rather than day 1.
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| Web link |
https://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F37046042%2F&data=05%7C01%7Catlas4%40uab.edu%7C11a3ea69cfd7486fb51708db7ef856ac%7Cd8999fe476af40b3b4351d8977abc08c%7C1%7C0%7C638243377289527056%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=p2ck8gArBJCY65cBrJdUxW7vYsEEI9CaDrUC%2BJmMLuc%3D&reserved=0
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| Contributor(s) |
Bachus H, McLaughlin E, Lewis C, Papillion AM, Benveniste EN, Hill DD, Rosenberg AF, Ballesteros-Tato A, León B |
| Citation(s) |
37046042 |
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| Submission date |
Aug 26, 2022 |
| Last update date |
Jul 07, 2023 |
| Contact name |
Dave Durell Hill |
| E-mail(s) |
[email protected]
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| Organization name |
University of Alabama at Birmingham
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| Department |
Microbiology
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| Street address |
1720 Second Avenue South
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35294 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| GSM6510400 |
D5, WT, 1 |
| GSM6510401 |
D5, WT, 2 |
| GSM6510402 |
D5, WT, 3 |
| GSM6510403 |
D3, IL6KO, 1 |
| GSM6510404 |
D3, IL6KO, 2 |
| GSM6510405 |
D3, IL6KO, 3 |
| GSM6510406 |
D5, IL6KO, 1 |
| GSM6510407 |
D5, IL6KO, 2 |
| GSM6510408 |
D5, IL6KO, 3 |
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| Relations |
| BioProject |
PRJNA874111 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212158_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE212158_leon2022_WT_IL6KO_cpm.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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