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| Status |
Public on Jun 13, 2020 |
| Title |
RNA-seq libraries for splenic and colonic MHCII+ APCs and colonic CD11b+, CD11c+, CD11b+CD11c+ MNP/DC |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The gut-brain axis, a reciprocal interaction between the central nervous system (CNS) and peripheral intestinal functions, is conceptually feasible from recent clinical and experimental evidence showing mutual interactions between the CNS and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel diseases (IBDs) and CNS disorders. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including induction and maintenance of peripheral regulatory T cells (pTregs) and what environmental cues prompt the host to protect host from development of IBDs. Here, we report a novel liver-brain-gut neural arc that ensures proper differentiation and maintenance of peripheral regulatory T cells (pTregs) in the gut. The hepatic vagal sensory afferents were responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius (NTS) of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level significantly impaired colonic pTregs, which was attributed to impairment of aldehyde dehydrogenase (ALDH) expression and retinoic acid (RA) synthesis by intestinal antigen-presenting cells (APCs). Muscarinic Ach receptor (mAChR) activation directly induced ALDH gene expression both in human and mouse colonic APCs, whereas genetic ablation of mAChRs abolished APC excitement in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in colitis models reduced the colonic pTreg pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver-brain-gut reflex arc tunes the number of pTregs and maintains the gut homeostasis. Intervening in this autonomic feedback feed-forward system could help develop new therapeutic strategies to treat or prevent immunological disorders of the gut.
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| Overall design |
RNA-seq was used for identifying signature genes of gut APCs including dendritic cells (DCs) and mononuclear phagocytes (MNPs). Specifically, RNA-seq libraries for splenic and colonic MHCII+ APCs and colonic CD11b+, CD11c+, CD11b+CD11c+ MNP/DC were generated from WT 8-wk-old mice.
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| Contributor(s) |
Mikami Y, Teratani T, Hagihara Y, Taniki N, Kanai T |
| Citation(s) |
32526765 |
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| Submission date |
Nov 25, 2019 |
| Last update date |
Aug 31, 2020 |
| Contact name |
Yohei Mikami |
| Organization name |
Keio University School of Medicine
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| Street address |
Shinanomachi 35
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| City |
Shinjuku-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
1608582 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA591565 |
| SRA |
SRP233187 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140952_RAW.tar |
8.5 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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