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Background. The vagal anti-inflammatory reflex is mediated by non-neuronal immune
cells that express Choline Acetyl Transferase (ChAT). ChAT catalyses the biosynthesis
and secretion of acetylcholine. In this study we characterize a novel population of
ChAT+ Th17 cells found in the intestine. Methods. We used ChAT(BAC)-eGFP reporter mice,
expressing eGFP under the control of ChAT promoter. CD45 + CD4+ cells from small intestine and colon were analysed by flow cytometry. In an in-vitro
antigen specific dendritic cell-T-cell assay, stimulation with an adrenergic receptor
agonist norepinephrine (NE) was tested. CD4-specific ChAT-/- mice were generated by
crossing CD4cre into ChATfl/fl. Intestinal microbiota was analysed using Illumina
sequencing. Results. Sorted intestinal CD4 + ChAT+ cells expressed elevated levels of IL-17, IL-22 and RORC compared with their CD4 + ChAT- counterparts, indicating that ChAT+ T-cells reflect Th17 cells. The generation of these cells is stimulated in-vitro
after activation of adrenergic receptors on dendritic cells. Interestingly, CD4ChAT-/-
mice displayed a reduced expression of antimicrobial peptides compared to ChATfl/fl
mice leading to increased microbial diversity and richness in the small intestine.
Conclusion. Our data provide evidence of cholinergic Th17 cells in the intestine,
which (1) respond to sympathetic input by up-regulating acetylcholine production,
and (2) drive antimicrobial peptide secretion, affecting microbial richness and diversity.
We provide evidence that autonomic dysfunction, as seen in patients with IBD, can
lead to intestinal dysbiosis through altered production of antimicrobial peptides
and thus contribute to pathophysiology of inflammatory disorders.
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