title: Cholinergic epithelial cell with chemosensory traits in murine thymic medulla.
abstract: Specialized epithelial cells with a tuft of apical microvilli ("brush cells") sense luminal content and initiate protective reflexes in response to potentially harmful substances. They utilize the canonical taste transduction cascade to detect "bitter" substances such as bacterial quorum-sensing molecules. In the respiratory tract, most of these cells are cholinergic and are approached by cholinoceptive sensory nerve fibers. Utilizing two different reporter mouse strains for the expression of choline acetyltransferase (ChAT), we observed intense labeling of a subset of thymic medullary cells. ChAT expression was confirmed by in situ hybridization. These cells showed expression of villin, a brush cell marker protein, and ultrastructurally exhibited lateral microvilli. They did not express neuroendocrine (chromogranin A, PGP9.5) or thymocyte (CD3) markers but rather thymic epithelial (CK8, CK18) markers and were immunoreactive for components of the taste transduction cascade such as Gα-gustducin, transient receptor potential melastatin-like subtype 5 channel (TRPM5), and phospholipase Cβ2. Reverse transcription and polymerase chain reaction confirmed the expression of Gα-gustducin, TRPM5, and phospholipase Cβ2. Thymic "cholinergic chemosensory cells" were often in direct contact with medullary epithelial cells expressing the nicotinic acetylcholine receptor subunit α3. These cells have recently been identified as terminally differentiated epithelial cells (Hassall's corpuscle-like structures in mice). Contacts with nerve fibers (identified by PGP9.5 and CGRP antibodies), however, were not observed. Our data identify, in the thymus, a previously unrecognized presumptive chemosensitive cell that probably utilizes acetylcholine for paracrine signaling. This cell might participate in intrathymic infection-sensing mechanisms.
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, Aulweg 123, 35385, Giessen, Germany.
authors.forename: Alexandra Regina
authors.initials: AR
authors.lastname: Panneck
authors.forename: Amir
authors.initials: A
authors.lastname: Rafiq
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schütz
authors.forename: Aichurek
authors.initials: A
authors.lastname: Soultanova
authors.forename: Klaus
authors.initials: K
authors.lastname: Deckmann
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chubanov
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
authors.forename: Gabriela
authors.initials: G
authors.lastname: Krasteva-Christ
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
authors.forename: Adriana
authors.initials: A
authors.lastname: del Rey
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002628:Chemoreceptor Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction; D013649:Taste; D013950:Thymus Gland / Q000166:cytology* / Q000294:innervation
chemical_list: D000109:Acetylcholine; D002795:Choline O-Acetyltransferase; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D011978:Receptors, Nicotinic; C485184:enhanced green fluorescent protein; C026615:villin