{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:04:09Z","timestamp":1790528649965,"version":"4.1.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2016_A90"],"award-info":[{"award-number":["2016_A90"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB-TR84"],"award-info":[{"award-number":["SFB-TR84"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHU1259\/10-1"],"award-info":[{"award-number":["SCHU1259\/10-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"Deutsche Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","award":["ALI-1.1"],"award-info":[{"award-number":["ALI-1.1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009560","name":"Uniklinikum Giessen und Marburg","doi-asserted-by":"publisher","award":["7\/2016"],"award-info":[{"award-number":["7\/2016"]}],"id":[{"id":"10.13039\/501100009560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009091","name":"Justus Liebig Universit\u00e4t Gie\u00dfen","doi-asserted-by":"publisher","award":["Young Researcher Grant"],"award-info":[{"award-number":["Young Researcher Grant"]}],"id":[{"id":"10.13039\/100009091","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Excellence Cluster Cardiopulmonary Institute","award":["EXC 147"],"award-info":[{"award-number":["EXC 147"]}]},{"name":"Projekt DEAL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cholinergic chemosensory cells (CCC) are infrequent epithelial cells with immunosensor function, positioned in mucosal epithelia preferentially near body entry sites in mammals including man. Given their adaptive capacity in response to infection and their role in combatting pathogens, we here addressed the time points of their initial emergence as well as their postnatal development from first exposure to environmental microbiota (i.e., birth) to adulthood in urethra and trachea, utilizing choline acetyltransferase (ChAT)-eGFP reporter mice, mice with genetic deletion of MyD88, toll-like receptor-2 (TLR2), TLR4, TLR2\/TLR4, and germ-free mice. Appearance of CCC differs between the investigated organs. CCC of the trachea emerge during embryonic development at E18 and expand further after birth. Urethral CCC show gender diversity and appear first at P6-P10 in male and at P11-P20 in female mice. Urethrae and tracheae of MyD88- and TLR-deficient mice showed significantly fewer CCC in all four investigated deficient strains, with the effect being most prominent in the urethra. In germ-free mice, however, CCC numbers were not reduced, indicating that TLR2\/4-MyD88 signaling, but not vita-PAMPs, governs CCC development. Collectively, our data show a marked postnatal expansion of CCC populations with distinct organ-specific features, including the relative impact of TLR2\/4-MyD88 signaling. Strong dependency on this pathway (urethra) correlates with absence of CCC at birth and gender-specific initial development and expansion dynamics, whereas moderate dependency (trachea) coincides with presence of first CCC at E18 and sex-independent further development.<\/jats:p>","DOI":"10.1007\/s00441-021-03424-9","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T14:03:31Z","timestamp":1614002611000},"page":"21-35","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Development of epithelial cholinergic chemosensory cells of the urethra and trachea of mice"],"prefix":"10.1007","volume":"385","author":[{"given":"Alexander","family":"Perniss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aichurek","family":"Soultanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Papadakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Dahlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Voigt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Sch\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3519-3837","authenticated-orcid":false,"given":"Klaus","family":"Deckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"3424_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S1074-7613(00)80596-8","volume":"9","author":"O Adachi","year":"1998","unstructured":"Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9:143\u2013150","journal-title":"Immunity"},{"key":"3424_CR2","doi-asserted-by":"crossref","unstructured":"Bankova LG, Dwyer DF, Yoshimoto E, Ualiyeva S, McGinty JW, Raff H, von Moltke J, Kanaoka Y, Frank Austen K, Barrett NA (2018) The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing airway brush cells leading to type 2 inflammation. Sci Immunol 3","DOI":"10.1126\/sciimmunol.aat9453"},{"key":"3424_CR3","doi-asserted-by":"publisher","first-page":"8287","DOI":"10.1073\/pnas.1402436111","volume":"111","author":"K Deckmann","year":"2014","unstructured":"Deckmann K, Filipski K, Krasteva-Christ G, Fronius M, Althaus M, Rafiq A, Papadakis T, Renno L, Jurastow I, Wessels L, Wolff M, Schutz B, Weihe E, Chubanov V, Gudermann T, Klein J, Bschleipfer T, Kummer W (2014) Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes. Proc Natl Acad Sci U S A 111:8287\u20138292","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR4","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s00418-016-1504-x","volume":"146","author":"K Deckmann","year":"2016","unstructured":"Deckmann K, Kummer W (2016) Chemosensory epithelial cells in the urethra: sentinels of the urinary tract. Histochem Cell Biol 146:673\u2013683","journal-title":"Histochem Cell Biol"},{"key":"3424_CR5","doi-asserted-by":"publisher","first-page":"8981","DOI":"10.1073\/pnas.1531172100","volume":"100","author":"TE Finger","year":"2003","unstructured":"Finger TE, Bottger B, Hansen A, Anderson KT, Alimohammadi H, Silver WL (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc Natl Acad Sci U S A 100:8981\u20138986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR6","doi-asserted-by":"crossref","unstructured":"Finger TE, Kinnamon SC (2011) Taste isn\u2019t just for taste buds anymore. F1000 Biol Rep 3:20","DOI":"10.3410\/B3-20"},{"key":"3424_CR7","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1002\/ar.1091880304","volume":"188","author":"WG Forssmann","year":"1977","unstructured":"Forssmann WG, Ito S, Weihe E, Aoki A, Dym M, Fawcett DW (1977) An improved perfusion fixation method for the testis. Anat Rec 188:307\u2013314","journal-title":"Anat Rec"},{"key":"3424_CR8","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature16527","volume":"529","author":"F Gerbe","year":"2016","unstructured":"Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I, Dardalhon V, Cesses P, Garnier L, Pouzolles M, Brulin B, Bruschi M, Harcus Y, Zimmermann VS, Taylor N, Maizels RM, Jay P (2016) Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529:226\u2013230","journal-title":"Nature"},{"key":"3424_CR9","doi-asserted-by":"publisher","first-page":"2929","DOI":"10.1152\/jn.00066.2008","volume":"99","author":"BD Gulbransen","year":"2008","unstructured":"Gulbransen BD, Clapp TR, Finger TE, Kinnamon SC (2008) Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro. J Neurophysiol 99:2929\u20132937","journal-title":"J Neurophysiol"},{"key":"3424_CR10","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s11068-005-5051-y","volume":"34","author":"BD Gulbransen","year":"2005","unstructured":"Gulbransen BD, Finger TE (2005) Solitary chemoreceptor cell proliferation in adult nasal epithelium. J Neurocytol 34:117\u2013122","journal-title":"J Neurocytol"},{"key":"3424_CR11","doi-asserted-by":"publisher","first-page":"e662","DOI":"10.1371\/journal.pone.0000662","volume":"2","author":"MM Heimesaat","year":"2007","unstructured":"Heimesaat MM, Fischer A, Siegmund B, Kupz A, Niebergall J, Fuchs D, Jahn HK, Freudenberg M, Loddenkemper C, Batra A, Lehr HA, Liesenfeld O, Blaut M, Gobel UB, Schumann RR, Bereswill S (2007) Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4. PLoS One 2:e662","journal-title":"PLoS One"},{"key":"3424_CR12","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1126\/science.aaf1648","volume":"351","author":"MR Howitt","year":"2016","unstructured":"Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV, Weinstock JV, Gallini CA, Redding K, Margolskee RF, Osborne LC, Artis D, Garrett WS (2016) Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351:1329\u20131333","journal-title":"Science"},{"key":"3424_CR13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/1297-9716-44-50","volume":"44","author":"KL Irvine","year":"2013","unstructured":"Irvine KL, Hopkins LJ, Gangloff M, Bryant CE (2013) The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6. Vet Res 44:50","journal-title":"Vet Res"},{"key":"3424_CR14","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/BF00318592","volume":"266","author":"S Iseki","year":"1991","unstructured":"Iseki S (1991) Postnatal development of the brush cells in the common bile duct of the rat. Cell Tissue Res 266:507\u2013510","journal-title":"Cell Tissue Res"},{"key":"3424_CR15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1471-2202-8-49","volume":"8","author":"S Kaske","year":"2007","unstructured":"Kaske S, Krasteva G, Konig P, Kummer W, Hofmann T, Gudermann T, Chubanov V (2007) TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8:49","journal-title":"BMC Neurosci"},{"key":"3424_CR16","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1073\/pnas.1019418108","volume":"108","author":"G Krasteva","year":"2011","unstructured":"Krasteva G, Canning BJ, Hartmann P, Veres TZ, Papadakis T, Muhlfeld C, Schliecker K, Tallini YN, Braun A, Hackstein H, Baal N, Weihe E, Schutz B, Kotlikoff M, Ibanez-Tallon I, Kummer W (2011) Cholinergic chemosensory cells in the trachea regulate breathing. Proc Natl Acad Sci U S A 108:9478\u20139483","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR17","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.lfs.2012.06.014","volume":"91","author":"G Krasteva","year":"2012","unstructured":"Krasteva G, Canning BJ, Papadakis T, Kummer W (2012) Cholinergic brush cells in the trachea mediate respiratory responses to quorum sensing molecules. Life Sci 91:992\u2013996","journal-title":"Life Sci"},{"key":"3424_CR18","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/s00418-012-0911-x","volume":"137","author":"G Krasteva","year":"2012","unstructured":"Krasteva G, Hartmann P, Papadakis T, Bodenbenner M, Wessels L, Weihe E, Schutz B, Langheinrich AC, Chubanov V, Gudermann T, Ibanez-Tallon I, Kummer W (2012) Cholinergic chemosensory cells in the auditory tube. Histochem Cell Biol 137:483\u2013497","journal-title":"Histochem Cell Biol"},{"key":"3424_CR19","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00418-012-0993-5","volume":"138","author":"G Krasteva","year":"2012","unstructured":"Krasteva G, Kummer W (2012) \u201cTasting\u201d the airway lining fluid. Histochem Cell Biol 138:365\u2013383","journal-title":"Histochem Cell Biol"},{"key":"3424_CR20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/MOU.0000000000000361","volume":"27","author":"W Kummer","year":"2017","unstructured":"Kummer W, Deckmann K (2017) Brush cells, the newly identified gatekeepers of the urinary tract. Curr Opin Urol 27:85\u201392","journal-title":"Curr Opin Urol"},{"key":"3424_CR21","doi-asserted-by":"publisher","first-page":"G285","DOI":"10.1152\/ajpgi.00073.2017","volume":"313","author":"M Middelhoff","year":"2017","unstructured":"Middelhoff M, Westphalen CB, Hayakawa Y, Yan KS, Gershon MD, Wang TC, Quante M (2017) Dclk1-expressing tuft cells: critical modulators of the intestinal niche? Am J Physiol Gastrointest Liver Physiol 313:G285\u2013G299","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"3424_CR22","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","volume":"560","author":"DT Montoro","year":"2018","unstructured":"Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, Rogel N, Burgin G, Tsankov AM, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Tata PR, Mou H, Shivaraju M, Bihler H, Mense M, Tearney GJ, Rowe SM, Engelhardt JF, Regev A, Rajagopal J (2018) A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560:319\u2013324","journal-title":"Nature"},{"issue":"33\u201341","key":"3424_CR23","first-page":"e37","volume":"49","author":"MS Nadjsombati","year":"2018","unstructured":"Nadjsombati MS, McGinty JW, Lyons-Cohen MR, Jaffe JB, DiPeso L, Schneider C, Miller CN, Pollack JL, Nagana Gowda GA, Fontana MF, Erle DJ, Anderson MS, Locksley RM, Raftery D, von Moltke J (2018) Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit. Immunity 49(33\u201341):e37","journal-title":"Immunity"},{"key":"3424_CR24","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/pr.2017.2","volume":"81","author":"DN O'Driscoll","year":"2017","unstructured":"O\u2019Driscoll DN, De Santi C, McKiernan PJ, McEneaney V, Molloy EJ, Greene CM (2017) Expression of X-linked Toll-like receptor 4 signaling genes in female vs. male neonates. Pediatr Res 81:831\u2013837","journal-title":"Pediatr Res"},{"key":"3424_CR25","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev-immunol-042718-041505","volume":"37","author":"CE O'Leary","year":"2019","unstructured":"O\u2019Leary CE, Schneider C, Locksley RM (2019) Tuft cells-systemically dispersed sensory epithelia integrating immune and neural circuitry. Annu Rev Immunol 37:47\u201372","journal-title":"Annu Rev Immunol"},{"key":"3424_CR26","doi-asserted-by":"publisher","first-page":"e11924","DOI":"10.1371\/journal.pone.0011924","volume":"5","author":"T Ogura","year":"2010","unstructured":"Ogura T, Krosnowski K, Zhang L, Bekkerman M, Lin W (2010) Chemoreception regulates chemical access to mouse vomeronasal organ: role of solitary chemosensory cells. PLoS One 5:e11924","journal-title":"PLoS One"},{"key":"3424_CR27","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1152\/jn.00186.2011","volume":"106","author":"T Ogura","year":"2011","unstructured":"Ogura T, Szebenyi SA, Krosnowski K, Sathyanesan A, Jackson J, Lin W (2011) Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells. J Neurophysiol 106:1274\u20131287","journal-title":"J Neurophysiol"},{"key":"3424_CR28","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1271\/bbb.130454","volume":"77","author":"M Ohmoto","year":"2013","unstructured":"Ohmoto M, Yamaguchi T, Yamashita J, Bachmanov AA, Hirota J, Matsumoto I (2013) Pou2f3\/Skn-1a is necessary for the generation or differentiation of solitary chemosensory cells in the anterior nasal cavity. Biosci Biotechnol Biochem 77:2154\u20132156","journal-title":"Biosci Biotechnol Biochem"},{"key":"3424_CR29","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s00441-014-2002-x","volume":"358","author":"AR Panneck","year":"2014","unstructured":"Panneck AR, Rafiq A, Schutz B, Soultanova A, Deckmann K, Chubanov V, Gudermann T, Weihe E, Krasteva-Christ G, Grau V, del Rey A, Kummer W (2014) Cholinergic epithelial cell with chemosensory traits in murine thymic medulla. Cell Tissue Res 358:737\u2013748","journal-title":"Cell Tissue Res"},{"key":"3424_CR30","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1038\/nature07830","volume":"458","author":"BS Park","year":"2009","unstructured":"Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458:1191\u20131195","journal-title":"Nature"},{"key":"3424_CR31","doi-asserted-by":"crossref","unstructured":"Rane CK, Jackson SR, Pastore CF, Zhao G, Weiner AI, Patel NN, Herbert DR, Cohen NA, Vaughan AE (2019) Development of solitary chemosensory cells in the distal lung after severe influenza injury. Am J Physiol Lung Cell Mol Physiol","DOI":"10.1152\/ajplung.00032.2019"},{"key":"3424_CR32","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1073\/pnas.1221655110","volume":"110","author":"C Reardon","year":"2013","unstructured":"Reardon C, Duncan GS, Brustle A, Brenner D, Tusche MW, Olofsson PS, Rosas-Ballina M, Tracey KJ, Mak TW (2013) Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proc Natl Acad Sci U S A 110:1410\u20131415","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR33","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/BF00345847","volume":"44","author":"J Rhodin","year":"1956","unstructured":"Rhodin J, Dalhamn T (1956) Electron microscopy of the tracheal ciliated mucosa in rat. Z Zellforsch Mikrosk Anat 44:345\u2013412","journal-title":"Z Zellforsch Mikrosk Anat"},{"key":"3424_CR34","unstructured":"Russell WMS, Burch RL (1959) The principles of humane experimental technique. Anim Welf Wheathampstead"},{"key":"3424_CR35","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nature10072","volume":"474","author":"LE Sander","year":"2011","unstructured":"Sander LE, Davis MJ, Boekschoten MV, Amsen D, Dascher CC, Ryffel B, Swanson JA, Muller M, Blander JM (2011) Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 474:385\u2013389","journal-title":"Nature"},{"key":"3424_CR36","doi-asserted-by":"publisher","first-page":"6075","DOI":"10.1073\/pnas.1402251111","volume":"111","author":"CJ Saunders","year":"2014","unstructured":"Saunders CJ, Christensen M, Finger TE, Tizzano M (2014) Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation. Proc Natl Acad Sci U S A 111:6075\u20136080","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR37","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1165\/rcmb.2012-0485OC","volume":"49","author":"CJ Saunders","year":"2013","unstructured":"Saunders CJ, Reynolds SD, Finger TE (2013) Chemosensory brush cells of the trachea. A stable population in a dynamic epithelium. Am J Respir Cell Mol Biol 49:190\u2013196","journal-title":"Am J Respir Cell Mol Biol"},{"key":"3424_CR38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/j.1469-7580.2005.00403.x","volume":"206","author":"A Sbarbati","year":"2005","unstructured":"Sbarbati A, Osculati F (2005) A new fate for old cells: brush cells and related elements. J Anat 206:349\u2013358","journal-title":"J Anat"},{"key":"3424_CR39","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1002\/ar.20866","volume":"292","author":"A Sbarbati","year":"2009","unstructured":"Sbarbati A, Tizzano M, Merigo F, Benati D, Nicolato E, Boschi F, Cecchini MP, Scambi I, Osculati F (2009) Acyl homoserine lactones induce early response in the airway. Anat Rec (Hoboken) 292:439\u2013448","journal-title":"Anat Rec (Hoboken)"},{"key":"3424_CR40","doi-asserted-by":"crossref","unstructured":"Schneider C, O'Leary CE, Locksley RM (2019) Regulation of immune responses by tuft cells. Nat Rev Immunol","DOI":"10.1038\/s41577-019-0176-x"},{"issue":"271\u2013284","key":"3424_CR41","first-page":"e214","volume":"174","author":"C Schneider","year":"2018","unstructured":"Schneider C, O\u2019Leary CE, von Moltke J, Liang HE, Ang QY, Turnbaugh PJ, Radhakrishnan S, Pellizzon M, Ma A, Locksley RM (2018) A metabolite-triggered tuft cell-ILC2 circuit drives small intestinal remodeling. Cell 174(271\u2013284):e214","journal-title":"Cell"},{"key":"3424_CR42","first-page":"87","volume":"6","author":"B Schutz","year":"2015","unstructured":"Schutz B, Jurastow I, Bader S, Ringer C, von Engelhardt J, Chubanov V, Gudermann T, Diener M, Kummer W, Krasteva-Christ G, Weihe E (2015) Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract. Front Physiol 6:87","journal-title":"Front Physiol"},{"key":"3424_CR43","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1097\/SHK.0b013e31802e40bd","volume":"27","author":"Z Spolarics","year":"2007","unstructured":"Spolarics Z (2007) The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection. Shock 27:597\u2013604","journal-title":"Shock"},{"key":"3424_CR44","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.4049\/jimmunol.1801069","volume":"202","author":"HA Ting","year":"2019","unstructured":"Ting HA, von Moltke J (2019) The immune function of tuft cells at gut mucosal surfaces and beyond. J Immunol 202:1321\u20131329","journal-title":"J Immunol"},{"key":"3424_CR45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1471-2466-11-3","volume":"11","author":"M Tizzano","year":"2011","unstructured":"Tizzano M, Cristofoletti M, Sbarbati A, Finger TE (2011) Expression of taste receptors in solitary chemosensory cells of rodent airways. BMC Pulm Med 11:3","journal-title":"BMC Pulm Med"},{"key":"3424_CR46","first-page":"51","volume":"28","author":"M Tizzano","year":"2013","unstructured":"Tizzano M, Finger TE (2013) Chemosensors in the nose: guardians of the airways. Physiol (Bethesda) 28:51\u201360","journal-title":"Physiol (Bethesda)"},{"key":"3424_CR47","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1073\/pnas.0911934107","volume":"107","author":"M Tizzano","year":"2010","unstructured":"Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A 107:3210\u20133215","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3424_CR48","doi-asserted-by":"crossref","unstructured":"Voigt A, Hubner S, Doring L, Perlach N, Hermans-Borgmeyer I, Boehm U, Meyerhof W (2015) cre-mediated recombination in Tas2r131 cells-A unique way to explore bitter taste receptor function inside and outside of the taste system. Chem Senses 40:627\u2013639","DOI":"10.1093\/chemse\/bjv049"},{"key":"3424_CR49","doi-asserted-by":"publisher","first-page":"5633","DOI":"10.1523\/JNEUROSCI.4647-06.2007","volume":"27","author":"J von Engelhardt","year":"2007","unstructured":"von Engelhardt J, Eliava M, Meyer AH, Rozov A, Monyer H (2007) Functional characterization of intrinsic cholinergic interneurons in the cortex. J Neurosci 27:5633\u20135642","journal-title":"J Neurosci"},{"key":"3424_CR50","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature16161","volume":"529","author":"J von Moltke","year":"2016","unstructured":"von Moltke J, Ji M, Liang HE, Locksley RM (2016) Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221\u2013225","journal-title":"Nature"},{"key":"3424_CR51","first-page":"367","volume":"5","author":"JQ Wang","year":"2014","unstructured":"Wang JQ, Jeelall YS, Ferguson LL, Horikawa K (2014) Toll-like receptors and cancer: MYD88 mutation and inflammation. Front Immunol 5:367","journal-title":"Front Immunol"},{"key":"3424_CR52","doi-asserted-by":"crossref","unstructured":"Wiederhold S, Papadakis T, Chubanov V, Gudermann T, Krasteva-Christ G, Kummer W (2015) A novel cholinergic epithelial cell with chemosensory traits in the murine conjunctiva. Int Immunopharmacol","DOI":"10.1016\/j.intimp.2015.06.027"},{"key":"3424_CR53","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1186\/1471-2164-13-335","volume":"13","author":"M Yamamoto","year":"2012","unstructured":"Yamamoto M, Yamaguchi R, Munakata K, Takashima K, Nishiyama M, Hioki K, Ohnishi Y, Nagasaki M, Imoto S, Miyano S, Ishige A, Watanabe K (2012) A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system development. BMC Genomics 13:335","journal-title":"BMC Genomics"},{"key":"3424_CR54","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s10735-017-9747-y","volume":"49","author":"Y Yamamoto","year":"2018","unstructured":"Yamamoto Y, Ozawa Y, Yokoyama T, Nakamuta N (2018) Immunohistochemical characterization of brush cells in the rat larynx. J Mol Histol 49:63\u201373","journal-title":"J Mol Histol"},{"key":"3424_CR55","doi-asserted-by":"publisher","first-page":"e0189340","DOI":"10.1371\/journal.pone.0189340","volume":"12","author":"J Yamashita","year":"2017","unstructured":"Yamashita J, Ohmoto M, Yamaguchi T, Matsumoto I, Hirota J (2017) Skn-1a\/Pou2f3 functions as a master regulator to generate Trpm5-expressing chemosensory cells in mice. PLoS One 12:e0189340","journal-title":"PLoS One"},{"key":"3424_CR56","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2119\/2006-00030.Zheng","volume":"12","author":"R Zheng","year":"2006","unstructured":"Zheng R, Pan G, Thobe BM, Choudhry MA, Matsutani T, Samy TS, Kang SC, Bland KI, Chaudry IH (2006) MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia. Mol Med 12:65\u201373","journal-title":"Mol Med"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-021-03424-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-021-03424-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-021-03424-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T18:04:44Z","timestamp":1626977084000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-021-03424-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["3424"],"URL":"https:\/\/doi.org\/10.1007\/s00441-021-03424-9","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"assertion":[{"value":"17 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}