The salivary gland ducts serve as an epithelial barrier between secretory components of the gland and the oral cavity. An essential function of such a barrier is the detection and response to external insults. In many tissues, scattered single chemosensory cells (SCCs) function as sentinels, which relay external cues into transduced signals that activate an immune response. In both mouse and human salivary glands, we have found distinct solitary duct cells that co-express components of chemosensory signaling pathways, including Nkcc1, IP3R3, and Plc2. In the mouse, these cells are marked by expression of the transcription factor Ascl3. The observation that these morphologically distinct cells exhibit molecular characteristics resembling SCCs suggests that they fulfill a specialized function. This proposal will explore our hypothesis that SCCs are active in mouse and human salivary glands, and are involved in detection and transduction of external stimuli to surrounding cells, and perhaps to neurons. We speculate that Ascl3 expression marks a type of SCCs in the mouse salivary gland, and will investigate whether this is the case in human glands as well. We expect that SCCs play a critical role in mounting an immune response in the salivary glands, and may be involved in the mechanisms leading to acute and chronic inflammation.

Public Health Relevance

Single chemosensory cells play a critical role in the immune response of tissues with epithelial barriers. Evidence for the presence of specialized secretory duct cells in the salivary glands suggests that such sentinel- like cells are likely important mediators of salivary inflammation. The identification of a unique cell type involved in protective immunity could help in understanding chronic inflammation or Sjgren?s syndrome in the salivary glands.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DE026861-02
Application #
9757746
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Chander, Preethi
Project Start
2018-08-07
Project End
2020-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627