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| Status |
Public on Sep 16, 2019 |
| Title |
Metabolite - sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deletion of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived IL-22 production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings demonstrate that Ffar2 regulates colonic ILC3 proliferation and function in a cell-intrinsic manner and identifies an ILC3-receptor signaling pathway regulating gut inflammatory tone and pathogen defense.
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| Overall design |
Colonic ILC3s (CD45+Lin- CD90.2+ NK1.1- NKp46+/- KLRG1-) were sorted from Ffar2-/- mice and littermate control WT mice. Two independent RNA-seq experiments were performed. (i.e. two biological replicates (sex-matched) for each group that contained RNA from pooled colonic ILC3s from 10 to 15 mice).
BioProject accession: PRJNA547949, SRA Study accession: SRP201015
Please note that the processed data files have been updated on Mar 12, 2020.
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| Contributor(s) |
Eunyoung C, Bae S, Garrett WS |
| Citation(s) |
31628054 |
| BioProject |
PRJNA547949 |
| |
| Submission date |
Sep 16, 2019 |
| Last update date |
Mar 12, 2020 |
| Contact name |
Sena Bae |
| E-mail(s) |
[email protected]
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| Phone |
617-432-3250
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| Organization name |
Harvard T.H. Chan School of Public Health
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| Lab |
665 Huntington Ave
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| Street address |
Boston
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| City |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| Relations |
| SRA |
SRP201015 |
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