Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity

Shobhit Dhawan, Giada de Palma, Rose A. Willemze, Francisca W. Hilbers, Caroline Verseijden, Misha D. Luyer, Sabine Nuding, Jan Wehkamp, Yuri Souwer, Esther C. de Jong, J. Seppen, René M. van den Wijngaard, Sven Wehner, Elena Verdu, Premek Bercik, Wouter J. de Jonge

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35 Citations (Scopus)


The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor (TNF) via acetylcholine-producing memory T cells in the spleen. These choline acetyltransferase (ChAT)-expressing T cells are also found in the intestine, where their function is unclear. We aimed to characterize these cells in mouse and human intestine and delineate their function. We made use of the ChAT-enhanced green fluorescent protein (eGFP) reporter mice. CD4Cre mice were crossed to ChATfl/fl mice to achieve specific deletion of ChAT in CD4+ T cells. We observed that the majority of ChAT-expressing T cells in the human and mouse intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC. The generation of ChAT-expressing T cells was skewed by dendritic cells after activation of their adrenergic receptor β2. To evaluate ChAT T cell function, we generated CD4-specific ChAT-deficient mice. CD4ChAT-/- mice showed a reduced level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which was associated with an enhanced bacterial diversity and richness in the small intestinal lumen in CD4ChAT-/- mice. We conclude that ChAT-expressing T cells in the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT-expressing T cells may function to mediate the host AMP secretion, microbial growth and expansion.

Original languageEnglish
Pages (from-to)G920-G933
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5
Publication statusPublished - 2016


  • Choline acetyltransferase positive
  • Vagal anti-inflammatory pathway

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