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| Status |
Public on Dec 12, 2019 |
| Title |
Enteric Nervous System Derived IL-18 Orchestrates Mucosal Barrier Immunity [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Using RNA sequencing, we report that neuron derived-IL-18 is required for intestinal antimicrobial protein expression
Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the anti-microbial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA-hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neurons alone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single cell sequencing revealed that enteric neuronal IL-18 is specifically required for homeostatic goblet cell AMP production. Together, we show that neuron derived IL-18 signaling controls tissue wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing.
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| Overall design |
For Bulk RnaSeq experiments proximal colons were removed from: 1) Il18f/f and Il18f/fHand2Cre+, 2) Il18f/f and Il18f/fVillinCre+, and 3) Il18f/f and Il18f/fFLK1Cre+ littermate mice and RNA extracted.
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| Contributor(s) |
Flavell RA |
| Citation missing |
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| |
| Submission date |
Dec 11, 2019 |
| Last update date |
Jan 28, 2020 |
| Contact name |
Richard Flavell |
| E-mail(s) |
richard.flavell@yale.edu
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| Organization name |
Yale University
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| Department |
Department of Immunobiology
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| Street address |
300 Cedar Street, TAC S-569
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| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06511 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE141810 |
Enteric Nervous System Derived IL-18 Orchestrates Mucosal Barrier Immunity |
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| Relations |
| BioProject |
PRJNA594861 |
| SRA |
SRP236593 |
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