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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 04, 2024 |
| Title |
RGS2 is an innate immune checkpoint for suppressing Gαq mediated IFNγ generation and lung injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Infections can trigger the release of IFNγ, a type II interferon, which exacerbates tissue inflammation and may lead to severe acute lung injury (ALI). However, the regulatory mechanisms of IFNγ production in the lungs are not fully understood. In this study, we identified RGS2 as a crucial regulator of IFNγ levels in the lungs during infection. The absence of RGS2 led to persistently elevated IFNγ production in macrophages, resulting in unresolved inflammatory lung damage. Notably, this effect was absent in RGS2-deficient chimeric mice that received wild-type bone marrow or RGS2 expression in alveolar macrophages (AMs), as well as in those treated with an IFNγ-blocking antibody. RGS2 exerts its regulatory role by inhibiting Gαq-mediated IFNγ production and inflammatory signaling in AMs. Consequently, the inhibition of Gαq in RGS2-deficient mice prevented IFNγ production in AMs and shifted their transcriptomic profile from an inflammatory to a reparative state. These findings suggest that the RGS2-Gαq signaling pathway could be a promising therapeutic target for mitigating inflammatory lung injury.
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| Overall design |
In this experiment, RNA sequencing (RNA-seq) was performed to investigate the transcriptomic effects of lipopolysaccharide (LPS)-induced inflammation in the lungs of wild-type (WT) and Rgs2 knockout (KO) mice. Bronchoalveolar lavage (BAL) collected 64 hours after LPS administration from both WT and Rgs2 KO mice, with or without treatment with the Gαq inhibitor (BIM-46187) (three mice per group pooled together). Total RNA was extracted using the RNeasy mini kit (Qiagen USA), and ribosomal RNA was depleted using the RiboMinus™ Eukaryote kit v2 (Thermo Fisher Scientific). RNA libraries were then constructed with the TruSeq RNA library prep kit v2 (Illumina) and sequenced using the NovaSeq 6000 platform with paired-end 150 bp reads.
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| Web link |
https://www.biorxiv.org/content/10.1101/2023.09.22.559016v1
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| Contributor(s) |
Joshi J, Joshi B, Zhang C, Banerjee S, Vellingiri V, Balaji Raghunathrao V, Anwar M, Rokade T, Zhang L, Amin R, Song Y, Mehta D |
| Citation(s) |
37790514 |
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| Submission date |
Sep 04, 2024 |
| Last update date |
Sep 04, 2024 |
| Contact name |
Vijay Avin Balaji Ragunathrao |
| Organization name |
University of Illinois at Chicago
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| Department |
Pharmacology and Regenerative Medicine
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| Lab |
E512
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| Street address |
835 S Wolcott Ave
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60612 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| GSM8496723 |
BAL, RGS2, LPS, 64h |
| GSM8496724 |
BAL, WT, BIM, LPS, 64h |
| GSM8496725 |
BAL, RGS2, BIM, LPS, 64h |
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| Relations |
| BioProject |
PRJNA1156693 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE276337_normalized_counts.txt.gz |
556.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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