Abstract
G protein-coupled taste receptors and their downstream signaling elements, including Gnat3 (also known as α-gustducin) and TrpM5, were first identified in taste bud cells. Subsequent studies, however, revealed that some cells in nongustatory tissues also express taste receptors and/or their signaling elements. These nongustatory-tissue-expressed taste receptors and signaling elements play important roles in a number of physiological processes, including metabolism and immune responses. Special populations of cells expressing taste signaling elements in nongustatory tissues have been described as solitary chemosensory cells (SCCs) and tuft cells, mainly based on their morphological features and their expression of taste signaling elements as a critical molecular signature. These cells are typically scattered in barrier epithelial tissues, and their functions were largely unknown until recently. Emerging evidence shows that SCCs and tuft cells play important roles in immune responses to microbes and parasites. Additionally, certain immune cells also express taste receptors or taste signaling elements, suggesting a direct link between chemosensation and immune function. In this chapter, we highlight our current understanding of the functional roles of these “taste-like” cells and taste signaling pathways in different tissues, focusing on their activities in immune regulation.
Keywords
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Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000) A novel family of mammalian taste receptors. Cell 100:693–702
Arid J, Antunes LAA, Koch LFA, Evangelista SS, Vasconcelos KRF, Brancher JA, Gabardo MCL, Milani AJ, Dutra ALT, Antunes LS, Vieira AR, Feltrin-Souza J, Küchler EC (2020) Association of taste receptor gene polymorphisms with dental caries. Braz Oral Res 34:e055. https://doi.org/10.1590/1807-3107bor-2020.vol34.0055
Bachmanov AA, Li X, Reed DR, Ohmen JD, Li S, Chen Z, Tordoff MG, de Jong PJ, Wu C, West DB, Chatterjee A, Ross DA, Beauchamp GK (2001) Positional cloning of the mouse saccharin preference (Sac) locus. Chem Senses 26:925–933. https://doi.org/10.1093/chemse/26.7.925s
Balic A, Harcus Y, Holland MJ, Maizels RM (2004) Selective maturation of dendritic cells by Nippostrongylus brasiliensis-secreted proteins drives Th2 immune responses. Eur J Immunol 34:3047–3059. https://doi.org/10.1002/eji.200425167
Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007. https://doi.org/10.1038/nature06196
Barontini J, Antinucci M, Tofanelli S, Cammalleri M, Dal Monte M, Gemignani F, Vodicka P, Marangoni R, Vodickova L, Kupcinskas J, Vymetalkova V, Forsti A, Canzian F, Stein A, Moreno V, Mastrodonato N, Tavano F, Panza A, Barale R, Landi S, Campa D (2017) Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer. BMC Gastroenterol 17:104. https://doi.org/10.1186/s12876-017-0659-9
Bezencon C, Furholz A, Raymond F, Mansourian R, Metairon S, Le Coutre J, Damak S (2008) Murine intestinal cells expressing Trpm5 are mostly brush cells and express markers of neuronal and inflammatory cells. J Comp Neurol 509:514–525. https://doi.org/10.1002/cne.21768
Bornstein C, Nevo S, Giladi A, Kadouri N, Pouzolles M, Gerbe F, David E, Machado A, Chuprin A, Toth B, Goldberg O, Itzkovitz S, Taylor N, Jay P, Zimmermann VS, Abramson J, Amit I (2018) Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells. Nature 559:622–626. https://doi.org/10.1038/s41586-018-0346-1
Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W (2002) The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet 32:397–401
Chamoun E, Mutch DM, Allen-Vercoe E, Buchholz AC, Duncan AM, Spriet LL, Haines J, Ma DWL, Guelph Family Health S (2018) A review of the associations between single nucleotide polymorphisms in taste receptors, eating behaviors, and health. Crit Rev Food Sci Nutr 58:194–207. https://doi.org/10.1080/10408398.2016.1152229
Cleenewerk L, Garssen J, Hogenkamp A (2020) Clinical use of Schistosoma mansoni antigens as novel immunotherapies for autoimmune disorders. Front Immunol 11:1821. https://doi.org/10.3389/fimmu.2020.01821
Daoudi H, Plesnik J, Sayed A, Sery O, Rouabah A, Rouabah L, Khan NA (2015) Oral fat sensing and CD36 gene polymorphism in Algerian lean and obese teenagers. Nutrients 7:9096–9104. https://doi.org/10.3390/nu7115455
Darby M, Schnoeller C, Vira A, Culley FJ, Bobat S, Logan E, Kirstein F, Wess J, Cunningham AF, Brombacher F, Selkirk ME, Horsnell WG (2015) The M3 muscarinic receptor is required for optimal adaptive immunity to helminth and bacterial infection. PLoS Pathog 11:e1004636. https://doi.org/10.1371/journal.ppat.1004636
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 111:8287–8292. https://doi.org/10.1073/pnas.1402436111
Devillier P, Naline E, Grassin-Delyle S (2015) The pharmacology of bitter taste receptors and their role in human airways. Pharmacol Ther 155:11–21. https://doi.org/10.1016/j.pharmthera.2015.08.001
Drayna D (2005) Human taste genetics. Annu Rev Genomics Hum Genet 6:217–235. https://doi.org/10.1146/annurev.genom.6.080604.162340
Du YW, Liu Q, Luo XC, Zhao DX, Xue JB, Feng P, Margolskee RF, Wang H, Huang L (2018) Effects of taste signaling protein abolishment on gut inflammation in an inflammatory bowel disease mouse model. J Vis Exp. https://doi.org/10.3791/58668
Dutta Banik D, Martin LE, Freichel M, Torregrossa AM, Medler KF (2018) TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proc Natl Acad Sci U S A 115:E772–E781. https://doi.org/10.1073/pnas.1718802115
El-Matary W, Bernstein CN (2020) Cancer risk in pediatric-onset inflammatory bowel disease. Front Pediatr 8:400. https://doi.org/10.3389/fped.2020.00400
El-Matary W, Moroz SP, Bernstein CN (2014) Inflammatory bowel disease in children of Manitoba: 30 years' experience of a tertiary center. J Pediatr Gastroenterol Nutr 59:763–766. https://doi.org/10.1097/MPG.0000000000000525
Eriksson L, Esberg A, Haworth S, Holgerson PL, Johansson I (2019) Allelic variation in taste genes is associated with taste and diet preferences and dental caries. Nutrients:11. https://doi.org/10.3390/nu11071491
Esberg A, Haworth S, Hasslof P, Lif Holgerson P, Johansson I (2020) Oral microbiota profile associates with sugar intake and taste preference genes. Nutrients 12. https://doi.org/10.3390/nu12030681
Feng P, Chai J, Yi H, Redding K, Margolskee RF, Huang L, Wang H (2018) Aggravated gut inflammation in mice lacking the taste signaling protein alpha-gustducin. Brain Behav Immun 71:23–27. https://doi.org/10.1016/j.bbi.2018.04.010
Finger TE, Böttger 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 100:8981–8986
Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC (2005) ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–1499. https://doi.org/10.1126/science.1118435
Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15:985–995. https://doi.org/10.1016/s1074-7613(01)00243-6
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 helminth parasites. Nature 529:226–230
Gil S, Coldwell S, Drury JL, Arroyo F, Phi T, Saadat S, Kwong D, Chung WO (2015) Genotype-specific regulation of oral innate immunity by T2R38 taste receptor. Mol Immunol 68:663–670. https://doi.org/10.1016/j.molimm.2015.10.012
Gonda TA, Tu S, Wang TC (2009) Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle 8:2005–2013. https://doi.org/10.4161/cc.8.13.8985
Grassin-Delyle S, Salvator H, Mantov N, Abrial C, Brollo M, Faisy C, Naline E, Couderc LJ, Devillier P (2019) Bitter taste receptors (TAS2Rs) in human lung macrophages: receptor expression and inhibitory effects of TAS2R agonists. Front Physiol 10:1267. https://doi.org/10.3389/fphys.2019.01267
Gurram RK, Zhu J (2019) Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses. Cell Mol Immunol 16:225–235. https://doi.org/10.1038/s41423-019-0210-8
Haber AL, Biton M, Rogel N, Herbst RH, Shekhar K, Smillie C, Burgin G, Delorey TM, Howitt MR, Katz Y, Tirosh I, Beyaz S, Dionne D, Zhang M, Raychowdhury R, Garrett WS, Rozenblatt-Rosen O, Shi HN, Yilmaz O, Xavier RJ, Regev A (2017) A single-cell survey of the small intestinal epithelium. Nature 551:333–339. https://doi.org/10.1038/nature24489
Harcus Y, Nicoll G, Murray J, Filbey K, Gomez-Escobar N, Maizels RM (2009) C-type lectins from the nematode parasites Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Parasitol Int 58:461–470. https://doi.org/10.1016/j.parint.2009.08.011
Hayes JE, Wallace MR, Knopik VS, Herbstman DM, Bartoshuk LM, Duffy VB (2011) Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults. Chem Senses 36:311–319. https://doi.org/10.1093/chemse/bjq132
Haznedaroglu E, Koldemir-Gunduz M, Bakir-Coskun N, Bozkus HM, Cagatay P, Susleyici-Duman B, Mentes A (2015) Association of sweet taste receptor gene polymorphisms with dental caries experience in school children. Caries Res 49:275–281. https://doi.org/10.1159/000381426
Hisatsune C, Yasumatsu K, Takahashi-Iwanaga H, Ogawa N, Kuroda Y, Yoshida R, Ninomiya Y, Mikoshiba K (2007) Abnormal taste perception in mice lacking the type 3 inositol 1,4,5-trisphosphate receptor. J Biol Chem 282:37225–37231. https://doi.org/10.1074/jbc.M705641200
Hofer D, Drenckhahn D (1992) Identification of brush cells in the alimentary and respiratory system by antibodies to villin and fimbrin. Histochemistry 98:237–242. https://doi.org/10.1007/BF00271037
Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol 13:1153–1158. https://doi.org/10.1016/s0960-9822(03)00431-7
Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS (1999) Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96:541–551. https://doi.org/10.1016/s0092-8674(00)80658-3
Hou JK, Abraham B, El-Serag H (2011) Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 106:563–573. https://doi.org/10.1038/ajg.2011.44
Howitt MR, Lavoie S, Michaud M, Blum AM, Tran SV, Weinstock JV, Gallini CA, Redding K, Margolskee RF, Osbourne LC, Artis D, Garrett WS (2016) Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351:1329–1333
Howitt MR, Cao YG, Gologorsky MB, Li JA, Haber AL, Biton M, Lang J, Michaud M, Regev A, Garrett WS (2020) The taste receptor TAS1R3 regulates small intestinal tuft cell homeostasis. ImmunoHorizons 4:23–32. https://doi.org/10.4049/immunohorizons.1900099
Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M, Margolskee RF (1999) Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci 2:1055–1062. https://doi.org/10.1038/15981
Imai H, Hakukawa M, Hayashi M, Iwatsuki K, Masuda K (2020) Expression of bitter taste receptors in the intestinal cells of non-human primates. Int J Mol Sci 21. https://doi.org/10.3390/ijms21030902
Ishimaru Y, Okada S, Naito H, Nagai T, Yasuoka A, Matsumoto I, Abe K (2005) Two families of candidate taste receptors in fishes. Mech Dev 122:1310–1321
Izakovicova Holla L, Borilova Linhartova P, Lucanova S, Kastovsky J, Musilova K, Bartosova M, Kukletova M, Kukla L, Dusek L (2015) GLUT2 and TAS1R2 polymorphisms and susceptibility to dental caries. Caries Res 49:417–424. https://doi.org/10.1159/000430958
Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, Kim HH, Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104:15069–15074. https://doi.org/10.1073/pnas.0706890104
Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621. https://doi.org/10.1146/annurev-immunol-030409-101225
Kitamoto S, Nagao-Kitamoto H, Jiao Y, Gillilland MG 3rd, Hayashi A, Imai J, Sugihara K, Miyoshi M, Brazil JC, Kuffa P, Hill BD, Rizvi SM, Wen F, Bishu S, Inohara N, Eaton KA, Nusrat A, Lei YL, Giannobile WV, Kamada N (2020) The intermucosal connection between the mouth and gut in commensal Pathobiont-driven colitis. Cell 182:447–462.e14. https://doi.org/10.1016/j.cell.2020.05.048
Kohanski MA, Workman AD, Patel NN, Hung LY, Shtraks JP, Chen B, Blasetti M, Doghramji L, Kennedy DW, Adappa ND, Palmer JN, Herbert DR, Cohen NA (2018) Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 142:460–469.e7. https://doi.org/10.1016/j.jaci.2018.03.019
Kokrashvili Z, Mosinger B, Margolskee RF (2009) Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr 90:822S–825S. https://doi.org/10.3945/ajcn.2009.27462T
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 108:9478–9483. https://doi.org/10.1073/pnas.1019418108
Kulkarni GV, Chng T, Eny KM, Nielsen D, Wessman C, El-Sohemy A (2013) Association of GLUT2 and TAS1R2 genotypes with risk for dental caries. Caries Res 47:219–225. https://doi.org/10.1159/000345652
Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, Abraham V, Doghramji L, Adappa ND, Palmer JN, Kennedy DW, Beauchamp GK, Doulias PT, Ischiropoulos H, Kreindler JL, Reed DR, Cohen NA (2012) T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest 122:4145–4159. https://doi.org/10.1172/JCI64240
Lee N, Jung YS, Lee HY, Kang N, Park YJ, Hwang JS, Bahk YY, Koo J, Bae YS (2014a) Mouse neutrophils express functional umami taste receptor T1R1/T1R3. BMB Rep 47:649–654. https://doi.org/10.5483/bmbrep.2014.47.11.185
Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B, Doghramji L, Xiong G, Adappa ND, Palmer JN, Kennedy DW, Kreindler JL, Margolskee RF, Cohen NA (2014b) Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest 124:1393–1405. https://doi.org/10.1172/JCI72094
Lei W, Ren W, Ohmoto M, Urban JF Jr, Matsumoto I, Margolskee RF, Jiang P (2018) Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine. Proc Natl Acad Sci U S A 115:5552–5557. https://doi.org/10.1073/pnas.1720758115
Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci U S A 100:15160–15165. https://doi.org/10.1073/pnas.2334159100
Lloyd CM, Snelgrove RJ (2018) Type 2 immunity: expanding our view. Sci Immunol 3. https://doi.org/10.1126/sciimmunol.aat1604
Luo XC, Chen ZH, Xue JB, Zhao DX, Lu C, Li YH, Li SM, Du YW, Liu Q, Wang P, Liu M, Huang L (2019) Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells. Proc Natl Acad Sci U S A 116:5564–5569. https://doi.org/10.1073/pnas.1812901116
Ma Z, Taruno A, Ohmoto M, Jyotaki M, Lim JC, Miyazaki H, Niisato N, Marunaka Y, Lee RJ, Hoff H, Payne R, Demuro A, Parker I, Mitchell CH, Henao-Mejia J, Tanis JE, Matsumoto I, Tordoff MG, Foskett JK (2018) CALHM3 is essential for rapid ion channel-mediated purinergic neurotransmission of GPCR-mediated tastes. Neuron 98:547–561.e10. https://doi.org/10.1016/j.neuron.2018.03.043
Malki A, Fiedler J, Fricke K, Ballweg I, Pfaffl MW, Krautwurst D (2015) Class I odorant receptors, TAS1R and TAS2R taste receptors, are markers for subpopulations of circulating leukocytes. J Leukoc Biol 97:533–545. https://doi.org/10.1189/jlb.2A0714-331RR
Margolskee RF (2002) Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem 277:1–4. https://doi.org/10.1074/jbc.R100054200
Matsumoto I, Ohmoto M, Narukawa M, Yoshihara Y, Abe K (2011) Skn-1a (Pou2f3) specifies taste receptor cell lineage. Nat Neurosci 14:685–687
Matsunami H, Montmayeur JP, Buck LB (2000) A family of candidate taste receptors in human and mouse. Nature 404:601–604. https://doi.org/10.1038/35007072
Maurer S, Wabnitz GH, Kahle NA, Stegmaier S, Prior B, Giese T, Gaida MM, Samstag Y, Hansch GM (2015) Tasting Pseudomonas aeruginosa biofilms: human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-Oxododecanoyl)-l-Homoserine lactone. Front Immunol 6:369. https://doi.org/10.3389/fimmu.2015.00369
Max M, Shanker YG, Huang L, Rong M, Liu Z, Campagne F, Weinstein H, Damak S, Margolskee RF (2001) Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet 28:58–63. https://doi.org/10.1038/ng0501-58
McGinty JW, Ting HA, Billipp TE, Nadjsombati MS, Khan DM, Barrett NA, Liang HE, Matsumoto I, von Moltke J (2020) Tuft-cell-derived leukotrienes drive rapid anti-helminth immunity in the small intestine but are dispensable for anti-protist immunity. Immunity 52:528–541.e7. https://doi.org/10.1016/j.immuni.2020.02.005
McLaughlin SK, McKinnon PJ, Margolskee RF (1992) Gustducin is a taste-cell-specific G protein closely related to the transducins. Nature 357:563–569. https://doi.org/10.1038/357563a0
McLean LP, Smith A, Cheung L, Urban JF Jr, Sun R, Grinchuk V, Desai N, Zhao A, Raufman JP, Shea-Donohue T (2016) Type 3 muscarinic receptors contribute to intestinal mucosal homeostasis and clearance of Nippostrongylus brasiliensis through induction of TH2 cytokines. Am J Physiol Gastrointest Liver Physiol 311:G130–G141. https://doi.org/10.1152/ajpgi.00461.2014
Mennella JA, Bobowski NK (2015) The sweetness and bitterness of childhood: insights from basic research on taste preferences. Physiol Behav 152:502–507. https://doi.org/10.1016/j.physbeh.2015.05.015
Miller CN, Proekt I, von Moltke J, Wells KL, Rajpurkar AR, Wang H, Rattay K, Khan IS, Metzger TC, Pollack JL, Fries AC, Lwin WW, Wigton EJ, Parent AV, Kyewski B, Erle DJ, Hogquist KA, Steinmetz LM, Locksley RM, Anderson MS (2018) Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development. Nature 559:627–631. https://doi.org/10.1038/s41586-018-0345-2
Montmayeur JP, Liberles SD, Matsunami H, Buck LB (2001) A candidate taste receptor gene near a sweet taste locus. Nat Neurosci 4:492–498. https://doi.org/10.1038/87440
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 560:319–324. https://doi.org/10.1038/s41586-018-0393-7
Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-kit(+)Sca-1(+) lymphoid cells. Nature 463:540–544. https://doi.org/10.1038/nature08636
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 49:33–41.e7. https://doi.org/10.1016/j.immuni.2018.06.016
Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367–1370. https://doi.org/10.1038/nature08900
Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS (2001) Mammalian sweet taste receptors. Cell 106:381–390
Ohmoto M, Matsumoto I, Yasuoka A, Yoshihara Y, Abe K (2008) Genetic tracing of the gustatory and trigeminal neural pathways originating from T1R3-expressing taste receptor cells and solitary chemoreceptor cells. Mol Cell Neurosci 38:505–517
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 Biotech Biochem 77:2154–2156
O'Leary CE, Schneider C, Locksley RM (2019) Tuft cells-systemically dispersed sensory epithelia integrating immune and neural circuitry. Annu Rev Immunol 37:47–72. https://doi.org/10.1146/annurev-immunol-042718-041505
Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, Kuo CJ (2009) Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15:701–706. https://doi.org/10.1038/nm.1951
Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Soderhall C, Pulkkinen V, Pedroletti C, Daham K, Kupczyk M, Dahlen B, Kere J, Dahlen SE, Hedlin G, Melen E (2013) Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J 42:65–78. https://doi.org/10.1183/09031936.00077712
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 358:737–748. https://doi.org/10.1007/s00441-014-2002-x
Patel NN, Kohanski MA, Maina IW, Triantafillou V, Workman AD, Tong CCL, Kuan EC, Bosso JV, Adappa ND, Palmer JN, Herbert DR, Cohen NA (2018) Solitary chemosensory cells producing interleukin-25 and group-2 innate lymphoid cells are enriched in chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. https://doi.org/10.1002/alr.22142
Pedersen N, Duricova D, Elkjaer M, Gamborg M, Munkholm P, Jess T (2010) Risk of extra-intestinal cancer in inflammatory bowel disease: meta-analysis of population-based cohort studies. Am J Gastroenterol 105:1480–1487. https://doi.org/10.1038/ajg.2009.760
Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5:1169–1176. https://doi.org/10.1038/nn952
Perniss A, Liu S, Boonen B, Keshavarz M, Ruppert AL, Timm T, Pfeil U, Soultanova A, Kusumakshi S, Delventhal L, Aydin O, Pyrski M, Deckmann K, Hain T, Schmidt N, Ewers C, Gunther A, Lochnit G, Chubanov V, Gudermann T, Oberwinkler J, Klein J, Mikoshiba K, Leinders-Zufall T, Offermanns S, Schutz B, Boehm U, Zufall F, Bufe B, Kummer W (2020) Chemosensory cell-derived acetylcholine drives tracheal Mucociliary clearance in response to virulence-associated formyl peptides. Immunity 52:683–699.e11. https://doi.org/10.1016/j.immuni.2020.03.005
Porter AJ, Wattchow DA, Brookes SJ, Schemann M, Costa M (1996) Choline acetyltransferase immunoreactivity in the human small and large intestine. Gastroenterology 111:401–408. https://doi.org/10.1053/gast.1996.v111.pm8690205
Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM (2010) Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci U S A 107:11489–11494. https://doi.org/10.1073/pnas.1003988107
Reed DR, McDaniel AH (2006) The human sweet tooth. BMC Oral Health 6(Suppl 1):S17. https://doi.org/10.1186/1472-6831-6-S1-S17
Robino A, Bevilacqua L, Pirastu N, Situlin R, Di Lenarda R, Gasparini P, Navarra CO (2015) Polymorphisms in sweet taste genes (TAS1R2 and GLUT2), sweet liking, and dental caries prevalence in an adult Italian population. Genes Nutr 10:485. https://doi.org/10.1007/s12263-015-0485-z
Rook GA (2012) Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol 42:5–15. https://doi.org/10.1007/s12016-011-8285-8
Roper SD, Chaudhari N (2017) Taste buds: cells, signals and synapses. Nat Rev Neurosci 18:485–497. https://doi.org/10.1038/nrn.2017.68
Rossler P, Kroner C, Freitag J, Noe J, Breer H (1998) Identification of a phospholipase C beta subtype in rat taste cells. Eur J Cell Biol 77:253–261. https://doi.org/10.1016/s0171-9335(98)80114-3
Rossler P, Boekhoff I, Tareilus E, Beck S, Breer H, Freitag J (2000) G protein betagamma complexes in circumvallate taste cells involved in bitter transduction. Chem Senses 25:413–421. https://doi.org/10.1093/chemse/25.4.413
Roudnitzky N, Behrens M, Engel A, Kohl S, Thalmann S, Hubner S, Lossow K, Wooding SP, Meyerhof W (2015) Receptor polymorphism and genomic structure interact to shape bitter taste perception. PLoS Genet 11:e1005530. https://doi.org/10.1371/journal.pgen.1005530
Rubin DC, Shaker A, Levin MS (2012) Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol 3:107. https://doi.org/10.3389/fimmu.2012.00107
Sainz E, Korley JN, Battey JF, Sullivan SL (2001) Identification of a novel member of the T1R family of putative taste receptors. J Neurochem 77:896–903. https://doi.org/10.1046/j.1471-4159.2001.00292.x
Sano T, Kim YJ, Oshima E, Shimizu C, Kiyonari H, Abe T, Higashi H, Yamada K, Hirabayashi Y (2011) Comparative characterization of GPRC5B and GPRC5CLacZ knockin mice; behavioral abnormalities in GPRC5B-deficient mice. Biochem Biophys Res Commun 412:460–465. https://doi.org/10.1016/j.bbrc.2011.07.118
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–265. https://doi.org/10.1038/nature07935
Schemann M, Sann H, Schaaf C, Mader M (1993) Identification of cholinergic neurons in enteric nervous system by antibodies against choline acetyltransferase. Am J Phys 265:G1005–G1009. https://doi.org/10.1152/ajpgi.1993.265.5.G1005
Schneider C, O'Leary 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 174:271–284 e14. https://doi.org/10.1016/j.cell.2018.05.014
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. https://doi.org/10.3389/fphys.2015.00087
Sell EA, Ortiz-Carpena JF, Herbert DR, Cohen NA (2020) Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol. https://doi.org/10.1016/j.anai.2020.10.011
Sotillo J, Sanchez-Flores A, Cantacessi C, Harcus Y, Pickering D, Bouchery T, Camberis M, Tang SC, Giacomin P, Mulvenna J, Mitreva M, Berriman M, LeGros G, Maizels RM, Loukas A (2014) Secreted proteomes of different developmental stages of the gastrointestinal nematode Nippostrongylus brasiliensis. Mol Cell Proteom MCP 13:2736–2751. https://doi.org/10.1074/mcp.M114.038950
Soultanova A, Voigt A, Chubanov V, Gudermann T, Meyerhof W, Boehm U, Kummer W (2015) Cholinergic chemosensory cells of the thymic medulla express the bitter receptor Tas2r131. Int Immunopharmacol 29:143–147. https://doi.org/10.1016/j.intimp.2015.06.005
Taruno A, Vingtdeux V, Ohmoto M, Ma Z, Dvoryanchikov G, Li A, Adrien L, Zhao H, Leung S, Abernethy M, Koppel J, Davies P, Civan MM, Chaudhari N, Matsumoto I, Hellekant G, Tordoff MG, Marambaud P, Foskett JK (2013) CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223–226. https://doi.org/10.1038/nature11906
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 107:3210–3215. https://doi.org/10.1073/pnas.0911934107
Tran HTT, Herz C, Ruf P, Stetter R, Lamy E (2018) Human T2R38 bitter taste receptor expression in resting and activated lymphocytes. Front Immunol 9:2949. https://doi.org/10.3389/fimmu.2018.02949
Trier JS, Allan CH, Marcial MA, Madara JL (1987) Structural features of the apical and tubulovesicular membranes of rodent small intestinal tuft cells. Anat Rec 219:69–77. https://doi.org/10.1002/ar.1092190112
Urban JF Jr, Noben-Trauth N, Donaldson DD, Madden KB, Morris SC, Collins M, Finkelman FD (1998) IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 8:255–264. https://doi.org/10.1016/s1074-7613(00)80477-x
von Moltke J, Ji M, Liang HE, Locksley RM (2016) Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529:221–225. https://doi.org/10.1038/nature16161
Wangchuk P, Kouremenos K, Eichenberger RM, Pearson M, Susianto A, Wishart DS, McConville MJ, Loukas A (2019) Metabolomic profiling of the excretory-secretory products of hookworm and whipworm. Metabolomics 15:101. https://doi.org/10.1007/s11306-019-1561-y
Wendell S, Wang X, Brown M, Cooper ME, DeSensi RS, Weyant RJ, Crout R, McNeil DW, Marazita ML (2010) Taste genes associated with dental caries. J Dent Res 89:1198–1202. https://doi.org/10.1177/0022034510381502
Yamaki M, Saito H, Isono K, Goto T, Shirakawa H, Shoji N, Satoh-Kuriwada S, Sasano T, Okada R, Kudoh K, Motoi F, Unno M, Komai M (2017) Genotyping analysis of bitter-taste receptor genes TAS2R38 and TAS2R46 in Japanese patients with gastrointestinal cancers. J Nutr Sci Vitaminol (Tokyo) 63:148–154. https://doi.org/10.3177/jnsv.63.148
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. https://doi.org/10.1371/journal.pone.0189340
Yarmolinsky DA, Zuker CS, Ryba NJ (2009) Common sense about taste: from mammals to insects. Cell 139:234–244. https://doi.org/10.1016/j.cell.2009.10.001
Yee KK, Li Y, Redding KM, Iwatsuki K, Margolskee RF, Jiang P (2013) Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue. Stem Cells 31:992–1000. https://doi.org/10.1002/stem.1338
Yoshida Y, Saitoh K, Aihara Y, Okada S, Misaka T, Abe K (2007) Transient receptor potential channel M5 and phospholipase C-β2 colocalizing in zebrafish taste receptor cells. Neuroreport 18:1517–1520
Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112:293–301. https://doi.org/10.1016/s0092-8674(03)00071-0
Zheng X, Tizzano M, Redding K, He J, Peng X, Jiang P, Xu X, Zhou X, Margolskee RF (2019) Gingival solitary chemosensory cells are immune sentinels for periodontitis. Nat Commun 10:4496. https://doi.org/10.1038/s41467-019-12505-x
Acknowledgments
We would like to thank Dr. Karen Yee at the Monell Chemical Senses Center for her help with the schematic illustration in Fig. 1. We thank Drs. Yoshio Hirabayashi and Jennifer Pluznick for sharing Gprc5c knockout mice (Accession number: CDB0485K; http://www.clst.riken.jp/arg/mutant%20mice%20list.html).
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Wang, H., Matsumoto, I., Jiang, P. (2021). Immune Regulatory Roles of Cells Expressing Taste Signaling Elements in Nongustatory Tissues. In: Palmer, R.K., Servant, G. (eds) The Pharmacology of Taste . Handbook of Experimental Pharmacology, vol 275. Springer, Cham. https://doi.org/10.1007/164_2021_468
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