Cholinergic chemosensory cells of the thymic medulla express the bitter receptor Tas2r131

Soultanova, Aichurek; Voigt, Anja; Chubanov, Vladimir; Gudermann, Thomas; Meyerhof, Wolfgang; Boehm, Ulrich; Kummer, Wolfgang

doi:10.1016/j.intimp.2015.06.005

Cited by 21 publications

(18 citation statements)

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“…Cortical and medullary thymic epithelial cells coordinate the development and repertoire of T cells in the thymus (Abramson and Anderson, 2017 ). Recently, cholinergic chemosensory cells have been reported in the thymus in ChAT- and Tas2r131 -reporter mice (Panneck et al, 2014 ; Soultanova et al, 2015 ). Also in Tas2r143 -reporter mice, EGFP-positive cells were detected in the thymus.…”

Section: Resultsmentioning

confidence: 99%

“…However, expression of individual bitter taste receptors has been less investigated. Transgenic mice indicating expression of Tas2r131 and Tas2r105 have shown that these receptors are expressed in the thymus, trachea, ovary, and testis as well as in the kidney, small intestine, and testis, respectively (Li and Zhou, 2012 ; Voigt et al, 2012 , 2015 ; Gu et al, 2015 ; Liu et al, 2015 ; Soultanova et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

Liu

et al. 2017

Front. Physiol.

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The mouse bitter taste receptors Tas2r143, Tas2r135, and Tas2r126 are encoded by genes that cluster on chromosome 6 and have been suggested to be expressed under common regulatory elements. Previous studies indicated that the Tas2r143/Tas2r135/Tas2r126 cluster is expressed in the heart, but other organs had not been systematically analyzed. In order to investigate the expression of this bitter taste receptor gene cluster in non-gustatory tissues, we generated a BAC (bacterial artificial chromosome) based transgenic mouse line, expressing CreERT2 under the control of the Tas2r143 promoter. After crossing this line with a mouse line expressing EGFP after Cre-mediated recombination, we were able to validate the Tas2r143-CreERT2 transgenic mouse line and monitor the expression of Tas2r143. EGFP-positive cells, indicating expression of members of the cluster, were found in about 47% of taste buds, and could also be found in several other organs. A population of EGFP-positive cells was identified in thymic epithelial cells, in the lamina propria of the intestine and in vascular smooth muscle cells of cardiac blood vessels. EGFP-positive cells were also identified in the epithelium of organs readily exposed to pathogens including lower airways, the gastrointestinal tract, urethra, vagina, and cervix. With respect to the function of cells expressing this bitter taste receptor cluster, RNA-seq analysis in EGFP-positive cells isolated from the epithelium of trachea and stomach showed expression of genes related to innate immunity. These data further support the concept that bitter taste receptors serve functions outside the gustatory system.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

Liu

et al. 2017

Front. Physiol.

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“…Although mTEC subsets I-III displayed transcriptional signatures correlating with immature progenitors, subset IV mature mTECsincluding Aire + cells and terminally differentiated post-Aire cellsagain provided a tuft cell-like signature. Although previous studies identified cells with molecular characteristics of chemosensory tuft cells in the thymus [27][28][29], the functional significance of these remains unclear. In this regard, the studies described above [21,26] suggest a functional significance of murine thymic tuft cells in the regulation of intrathymic type 2 innate lymphoid cells (ILC2s) and iNKT2 cells, where diphtheria toxin-mediated ablation of post-Aire tuft cells in mice expressing the diphtheria toxin receptor under the control of the Aire promoter led to reduced intrathymic iNKT2 numbers relative to controls; moreover, the absence of Pou2f3dependent tuft cells in the thymus of Pou2f3-deficient mice resulted in increased numbers of ILC2 cells relative to controls [21,26].…”

Section: New Complexity In Medullary Thymic Epitheliummentioning

confidence: 99%

Rethinking Thymic Tolerance: Lessons from Mice

Inglesfield

Cosway

Jenkinson

et al. 2019

Trends in Immunology

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In the thymus, distinct cortex and medulla areas emphasize the division of labor in selection events shaping the abT cell receptor repertoire. For example, MHC restriction via positive selection is a unique property of epithelial cells in the thymic cortex. Far less clear are the events controlling tolerance induction in the medulla. By acting in concert through multiple roles, including antigen production/presentation and chemokine-mediated control of migration, we propose that medullary epithelium and dendritic cells collectively enable the medulla to balance T cell production with negative selection and Foxp3 + regulatory T cell (Treg) development. We examine here the features of these medullary resident cells and their roles in T cell tolerance, and discuss how imbalance in the thymus can result in loss of T cell tolerance. Thymic Medulla and the Control of T Cell ToleranceThe thymus produces multiple T cell types that play key roles in both innate and adaptive immune responses. The importance of these responses has now been shown in sister lineages of vertebrates, long after the function of the thymus was proven for jawed vertebrates in the 1960s [1,2]. Indeed, a key feature of adaptive immunity lies in its ability to generate a wide diversity of antigen receptors that target non-self. For T cells, this is achieved by T cell receptor (TCR) gene rearrangements that take place during T cell development in the thymus. Because of the random nature of gene rearrangement, the thymus imposes stringent mechanisms that shape the abTCR repertoire. Such processes are crucial because they ensure that abT cells (see Glossary) leaving the thymus are not only biased towards the recognition of self-MHC proteins but also tolerant to self-antigens. To achieve this the thymus creates a division of labor: the cortex imposes MHC restriction via positive selection, while the medulla imposes T cell tolerance via a combination of negative selection and Foxp3 + Treg development.The generation of abT cells in the thymus involves immature thymocytes being subjected to sequential checkpoints as they undergo intrathymic migration. To ensure that the thymus produces abT cells capable of antigen recognition in peripheral tissues, the cortex supports positive selection of immature CD4 + CD8 + double-positive (DP) thymocytes that recognize selfpeptide/MHC complexes produced and expressed by cortical thymic epithelial cells (cTECs). This process rescues DP thymocytes from cell death and triggers further differentiation, including expression of the chemokine receptor CCR7 that guides newly selected thymocytes into the medulla [3,4].Because positive selection results in the survival of thymocytes that recognize self-peptide/ MHC, additional selection mechanisms ensure that T cell development produces functional thymocytes that are tolerant to self-antigens. The thymic medulla provides a specialized microenvironment to support these events, and medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) combine to enforce two key proces...

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“…Furthermore, mTAS2Rs are expressed in cholinergic cells of the thymic medulla (Soultanova et al . ), suggesting a regulatory role during the maturation process of T‐cells. TAS2Rs thus appear to have a modulatory role on immune activation, which may make them therapeutic targets for the treatment of allergy, and more specifically, given their effects on bronchorelaxation, allergic asthma.…”

Section: Expression and Function Of Extra‐oral Bitter Taste Receptorsmentioning

confidence: 99%

“…hTAS2Rs are also present on mast cells, and the TAS2R agonists DB, chloroquine, dextromethrophan and noscapine inhibit IgE-induced release of histamine and prostaglandin D 2 (Ekoff et al 2014). Furthermore, mTAS2Rs are expressed in cholinergic cells of the thymic medulla (Soultanova et al 2015), suggesting a regulatory role during the maturation process of T-cells. TAS2Rs thus appear to have a modulatory role on immune activation, which may make them therapeutic targets for the treatment of allergy, and more specifically, given their effects on bronchorelaxation, allergic asthma.…”

Section: A Role For Bitter Taste Receptors In Internal Organs?mentioning

confidence: 99%

The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity

Avau

Depoortere

2015

Acta Physiologica

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The bitter taste receptor (TAS2R)-family of G-protein-coupled receptors has been identified on the tongue as detectors of bitter taste over a decade ago. In the last few years, they have been discovered in an ever growing number of extra-oral tissues, including the airways, the gut, the brain and even the testis. In tissues that contact the exterior, protective functions for TAS2Rs have been proposed, in analogy to their function on the tongue as toxicity detector. However, TAS2Rs have also been found in internal organs, suggesting other roles for these receptors, perhaps involving as yet unidentified endogenous ligands. The current review gives an overview of the different proposed functions for TAS2Rs in tissues other than the oral cavity; from appetite regulation to the treatment of asthma, regulation of gastrointestinal motility and control of airway innate immunity.

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Cholinergic chemosensory cells of the thymic medulla express the bitter receptor Tas2r131

Cited by 21 publications

References 30 publications

Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

Members of Bitter Taste Receptor Cluster Tas2r143/Tas2r135/Tas2r126 Are Expressed in the Epithelium of Murine Airways and Other Non-gustatory Tissues

Rethinking Thymic Tolerance: Lessons from Mice

The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity

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