title: Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity.
abstract: 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. CD4Cremice were crossed to ChATfl/flmice 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 β2To 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.
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: Shobhit
authors: S
authors: Dhawan
authors: Farncombe Institute, McMaster University, Hamilton, Ontario, Canada.
authors: Giada
authors: G
authors: De Palma
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: Rose A
authors: RA
authors: Willemze
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: Francisca W
authors: FW
authors: Hilbers
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: Caroline
authors: C
authors: Verseijden
authors: Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
authors: Misha D
authors: MD
authors: Luyer
authors: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Stuttgart, Germany.|University of Tübingen, Tübingen, Germany.
authors: Sabine
authors: S
authors: Nuding
authors: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, Stuttgart, Germany.|University of Tübingen, Tübingen, Germany.
authors: Jan
authors: J
authors: Wehkamp
authors: Department of Cell Biology and Histology, Academic Medical Centrum, Amsterdam, The Netherlands; and.
authors: Yuri
authors: Y
authors: Souwer
authors: Department of Cell Biology and Histology, Academic Medical Centrum, Amsterdam, The Netherlands; and.
authors: Esther C
authors: EC
authors: de Jong
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: J
authors: J
authors: Seppen
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
authors: René M
authors: RM
authors: van den Wijngaard
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.|Department of Surgery, University of Bonn, Bonn, Germany.
authors: Sven
authors: S
authors: Wehner
authors: Farncombe Institute, McMaster University, Hamilton, Ontario, Canada.
authors: Elena
authors: E
authors: Verdu
authors: Farncombe Institute, McMaster University, Hamilton, Ontario, Canada.
authors: Premek
authors: P
authors: Bercik
authors: Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands; W.j.dejonge@amc.nl.
authors: Wouter J
authors: WJ
authors: de Jonge
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D023082:Defensins / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D023082:Defensins; C058181:insect defensin A; D002795:Choline O-Acetyltransferase; C519253:Ang4 protein, mouse; D012259:Ribonuclease, Pancreatic; D009113:Muramidase; D000109:Acetylcholine
keywords: choline acetyltransferase positive; vagal anti-inflammatory pathway