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  Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters

Keshavarz, M., Tabrizi, S. F., Ruppert, A.-L., Pfeil, U., Schreiber, Y., Klein, J., et al. (2022). Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters. SCIENCE IMMUNOLOGY, 7(69): eabf6734. doi:10.1126/sciimmunol.abf6734.

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 Creators:
Keshavarz, Maryam, Author
Tabrizi, Schayan Faraj, Author
Ruppert, Anna-Lena, Author
Pfeil, Uwe, Author
Schreiber, Yannick, Author
Klein, Jochen, Author
Brandenburger, Isabell1, Author           
Lochnit, Guenter, Author
Bhushan, Sudhanshu, Author
Perniss, Alexander, Author
Deckmann, Klaus, Author
Hartmann, Petra, Author
Meiners, Mirjam, Author
Mermer, Petra, Author
Rafiq, Amir, Author
Winterberg, Sarah, Author
Papadakis, Tamara, Author
Thomas, Dominique, Author
Angioni, Carlo, Author
Oberwinkler, Johannes, Author
Chubanov, Vladimir, AuthorGudermann, Thomas, AuthorGaertner, Ulrich, AuthorOffermanns, Stefan1, Author           Schuetz, Burkhard, AuthorKummer, Wolfgang, Author more..
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: The gallbladder stores bile between meals and empties into the duodenum upon demand and is thereby exposed to the intestinal microbiome. This exposure raises the need for antimicrobial factors, among them, mucins produced by cholangiocytes, the dominant epithelial cell type in the gallbladder. The role of the much less frequent biliary tuft cells is still unknown. We here show that propionate, a major metabolite of intestinal bacteria, activates tuft cells via the short-chain free fatty acid receptor 2 and downstream signaling involving the cation channel transient receptor potential cation channel subfamily M member 5. This results in corelease of acetylcholine and cysteinyl leukotrienes from tuft cells and evokes synergistic paracrine effects upon the epithelium and the gallbladder smooth muscle, respectively. Acetylcholine triggers mucin release from cholangiocytes, an epithelial defense mechanism, through the muscarinic acetylcholine receptor M3. Cysteinyl leukotrienes cause gallbladder contraction through their cognate receptor CysLTR1, prompting emptying and closing. Our results establish gallbladder tuft cells as sensors of the microbial metabolite propionate, initiating dichotomous innate defense mechanisms through simultaneous release of acetylcholine and cysteinyl leukotrienes.

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 Dates: 2022-03-04
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: ISI: 000787871500007
DOI: 10.1126/sciimmunol.abf6734
PMID: 35245090
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Title: SCIENCE IMMUNOLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 7 (69) Sequence Number: eabf6734 Start / End Page: - Identifier: ISSN: 2470-9468