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

First Author  Dhawan S Year  2016
Journal  Am J Physiol Gastrointest Liver Physiol Volume  311
Issue  5 Pages  G920-G933
PubMed ID  27514477 Mgi Jnum  J:240320
Mgi Id  MGI:5883144 Doi  10.1152/ajpgi.00114.2016
Citation  Dhawan S, et al. (2016) Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity. Am J Physiol Gastrointest Liver Physiol 311(5):G920-G933
abstractText  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 beta2 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.
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