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| Status |
Public on May 20, 2024 |
| Title |
Mast Cells Control Lung Type 2 Inflammation via Prostaglandin E2-Driven Soluble ST2. |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Severe asthma and sinus disease is a consequence of Type 2 inflammation (T2I), mediated by IL-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E2 (PGE2) drives production of sST2 to limit features of lung T2I. PGE2 deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE2 metabolites correlate with serum sST2. In mice, PGE2 enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs or EP2 receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE2 or ST2 expression by MCs back to control levels. PGE2 deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE2 thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE2 states.
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| Overall design |
RNA-seq analysis of Mouse Bone Marrow MCs were stimulated with 10 ng/mL of IL-33 and/or 1 µM of PGE2 for 24 hours
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| Contributor(s) |
Dwyer D, Alhallak K, Boyce J |
| Citation missing |
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| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U19 AI095219 |
Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease |
BRIGHAM AND WOMEN'S HOSPITAL |
Joshua A Boyce |
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| |
| Submission date |
May 03, 2024 |
| Last update date |
May 20, 2024 |
| Contact name |
Daniel Dwyer |
| E-mail(s) |
dfdwyer@bwh.harvard.edu
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| Organization name |
Brigham and Women's Hospital
|
| Street address |
60 Fenwood Road
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA1107468 |
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