{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:55:32Z","timestamp":1792468532447,"version":"4.5.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"69","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,3,25]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1126\/sciimmunol.abf6734","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T18:57:36Z","timestamp":1646420256000},"source":"Crossref","is-referenced-by-count":54,"title":["Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-2508","authenticated-orcid":true,"given":"Maryam","family":"Keshavarz","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schayan","family":"Faraj Tabrizi","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Pfeil","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group TMP, Frankfurt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6971-3381","authenticated-orcid":true,"given":"Jochen","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Goethe University Frankfurt, Frankfurt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabell","family":"Brandenburger","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0377-395X","authenticated-orcid":true,"given":"G\u00fcnter","family":"Lochnit","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9088-8108","authenticated-orcid":true,"given":"Sudhanshu","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Perniss","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3519-3837","authenticated-orcid":true,"given":"Klaus","family":"Deckmann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7353-0884","authenticated-orcid":true,"given":"Mirjam","family":"Meiners","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Mermer","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Rafiq","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Winterberg","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-3669","authenticated-orcid":true,"given":"Dominique","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pharmazentrum Frankfurt\/ZAFES, Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, Germany."},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8484-7767","authenticated-orcid":true,"given":"Carlo","family":"Angioni","sequence":"additional","affiliation":[{"name":"Pharmazentrum Frankfurt\/ZAFES, Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-3626","authenticated-orcid":true,"given":"Johannes","family":"Oberwinkler","sequence":"additional","affiliation":[{"name":"Philipps-Universit\u00e4t Marburg, Institut f\u00fcr Physiologie und Pathophysiologie, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Chubanov","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology, German Center for Lung Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-7965","authenticated-orcid":true,"given":"Thomas","family":"Gudermann","sequence":"additional","affiliation":[{"name":"Walther Straub Institute of Pharmacology and Toxicology, German Center for Lung Research, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-6805","authenticated-orcid":true,"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4473-1959","authenticated-orcid":true,"given":"Burkhard","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-0683","authenticated-orcid":true,"given":"Wolfgang","family":"Kummer","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University Giessen, Giessen, Germany."},{"name":"Excellence Cluster Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c150050"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00307090"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801069"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-49"},{"key":"e_1_3_3_6_2","first-page":"87","article-title":"Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract","volume":"6","author":"Sch\u00fctz B.","year":"2015","unstructured":"B. Sch\u00fctz, I. Jurastow, S. Bader, C. Ringer, J. von Engelhardt, V. Chubanov, T. Gudermann, M. Diener, W. Kummer, G. Krasteva-Christ, E. Weihe, Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract. Front. Physiol. 6, 87 (2015).","journal-title":"Front. Physiol."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.06.016"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0176-x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16527"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.02.005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.02.011"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402251111"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1668"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-15-13"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(79)90342-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.2.643"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.28.111"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(83)90043-6"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53997-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21768"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aax7224"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/343282a0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12665"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13589"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211609200"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301403200"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.07.002"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720758115"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1159\/000144796"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300468-JLR200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens2010055"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.36.1.407-416.1982"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402436111"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011924"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.28.10.1221"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2015.12.009"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-3295"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006129"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38628-1"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.01.002"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-66"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2820"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3779"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01020-6"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.122"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.08.007"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01900817"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.2.G437"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.10.011"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2017.06.002"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2013686117"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.abf6734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T10:43:32Z","timestamp":1705401812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abf6734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":51,"journal-issue":{"issue":"69","published-print":{"date-parts":[[2022,3,25]]}},"alternative-id":["10.1126\/sciimmunol.abf6734"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.abf6734","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,25]]},"article-number":"eabf6734"}}