Presentation Details
| Tissue resident CD8+ T cell-mediated inflammation drives bitter sensitivity Pavel Nesmiyanov, Flavia Saavedra, J.Michael Stolley. Cleveland Clinic Research, Department of Inflammation & Immunity, Cleveland, OH, USA |
Abstract
Tissue-resident memory CD8⁺ T cells (CD8⁺ TRM) provide durable frontline protection at barrier mucosal sites commonly exploited by pathogens as portals of entry. While extensively studied in several mucosal tissues including the gut, lungs, and urogenital mucosa, comparatively little is known about CD8+ TRM biology in the oral mucosa. To address this knowledge gap, we developed a model for establishing abundant antigen-specific CD8⁺ TRM in the oral mucosa of mice (oral CD8+ TRM). Histological studies identified that oral CD8⁺ TRM were disproportionately associated with taste papillae and isolated taste buds of the soft palate, where their local reactivation via swabbing with viral peptides triggered robust immune cell accumulation and mobilization into taste buds. Based on these observations, we hypothesized that oral CD8+ TRM recall responses may impact taste perception. To begin addressing this, bulk RNAseq was first performed on taste tissues isolated from mice receiving oral CD8+ TRM reactivation 12H earlier, where transcriptional upregulation of multiple Tas2r (bitter) genes were noted. Based on these findings, brief access taste testing was subsequently performed using the bitter tastant quinine, where we found that oral CD8+ TRM reactivation increased aversive behavior at low and intermediate concentrations. Prophylactic depletion of oral CD8+ TRM prior to testing abolished this response. Collectively, we provide evidence that oral CD8+ TRM reactivation amplifies bitter sensitivity. Future work will assess whether this phenomenon extends to other taste modalities.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.