RRC ID 80818
著者 Liu J, Zhang P, Zheng Z, Afridi MI, Zhang S, Wan Z, Zhang X, Stingelin L, Wang Y, Tu H.
タイトル GABAergic signaling between enteric neurons and intestinal smooth muscle promotes innate immunity and gut defense in Caenorhabditis elegans.
ジャーナル Immunity
Abstract The nervous system is critical for intestinal homeostasis and function, but questions remain regarding its impact on gut immune defense. By screening the major neurotransmitters of C. elegans, we found that γ-aminobutyric acid (GABA) deficiency enhanced susceptibility to pathogenic Pseudomonas aeruginosa PA14 infection. GABAergic signaling between enteric neurons and intestinal smooth muscle promoted gut defense in a PMK-1/p38-dependent, but IIS/DAF-16- and DBL-1/TGF-β-independent, pathway. Transcriptomic profiling revealed that the neuropeptide, FLP-6, acted downstream of enteric GABAergic signaling. Further data determined that FLP-6 was expressed and secreted by intestinal smooth muscle cells and functioned as a paracrine molecule on the intestinal epithelium. FLP-6 suppressed the transcription factors ZIP-10 and KLF-1 that worked in parallel and converged to the PMK-1/p38 pathway in the intestinal epithelia for innate immunity and gut defense. Collectively, these findings uncover an enteric neuron-muscle-epithelium axis that may be evolutionarily conserved in higher organisms.
巻・号 56(7)
ページ 1515-1532.e9
公開日 2023-7-11
DOI 10.1016/j.immuni.2023.06.004
PII S1074-7613(23)00261-3
PMID 37437538
MeSH Animals Caenorhabditis elegans* Immunity, Innate Muscle, Smooth Neurons* Signal Transduction
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リソース情報
線虫 tm1406 tm1165 tm4085 tm5156 tm2105 tm1712