Chemosensory cholinergic signaling network in the thymic medullary epithelium

Cholinergic signaling influences T cell maturation, and acetylcholine is endogenously synthesized in the thymus. Utilizing a reporter mouse strain that expresses GFP under the promoter of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), we detected cholinergic cells in the thymic medulla. Using additional reporter mouse strains and immunohistochemistry, we show that ChAT-positive cells co-express the bitter taste receptor Tas2R131 and the components of taste signaling cascade α-gustducin, phospholipase Cβ2 and the cation channel TRPM5. These thymic cholinergic chemosensory cells are different from the stellate medullary thymic epithelial cells (mTEC) involved in intrathymic negative selection of thymocytes in that they do not express autoimmune regulator (AIRE) and express cortical (8/18) instead of medullary (5/14) keratins. They are not approached by cholinoceptive sensory nerve fibers. Instead, they are in proximity to terminally differentiated (keratin 10-positive, Hassall-like bodies) mTEC carrying nicotinic acetylcholine receptors (α3-subunit). In human newborn thymus, these cells closely surround or are integrated in the outer layer of the Hassall's corpuscles. Similar cells in mucosal surfaces have been associated with detection of bacterial products. Hence, we quantified thymic mRNA expression of an array of genes involved in cholinergic and chemosensory transmission in streptococcal pneumonia-infected mice, which revealed 6 – 9fold up-regulation of TRPM5 and α-gustducin. In conclusion, we identified a novel chemosensory cholinergic cell type in the thymic medulla and hypothesize that there is a paracrine acetylcholine signaling between these cells and Hassall's corpuscles, and that this signaling plays a role in bacterial pathogen detection and defense.

*Presenting author