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Mucosal Immune Surveillance at the Taste Papillae

Award Number: R03DE032417
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Mucosal Immune Surveillance at the Taste Papillae - Project Summary Taste buds are continually exposed to oral and food borne microbes, but the pathways underlying the three- way interactions between taste cells, the oral microbiome and oral epithelial immune cells have not been studied in sufficient detail. While the vast majority of the hundreds of microbial species in the oral cavity are either innocuous or beneficial to the host, dysregulation of the oral microbiome can cause taste disorders. Infection associated taste loss is observed in the cases of COVID-19, viral hepatitis, influenza, and candidiasis, to name a few examples. Mucosae such as those in the gut and tonsils possess secondary lymphoid tissues called mucosae associated lymphoid tissue (MALT) over laid by specialized epithelia call the follicle associated epithelium (FAE). FAE contain immune surveillance cells called microfold cells (M cells) that transcytose luminal microbes and present them to immune cells in the underlying germinal centers, that generate an appropriate immune response. Thus, M cells are central players in mucosal immunity, and dysregulation of M cell pathways are known to cause infection. Using single cell RNASeq, we discovered that sweet taste receptor cells (STRCs) and duct cells of the von Ebner gland (VDCs), a minor salivary gland associated with taste papillae, express several M cell marker genes, including Spib, a transcription factor required for M cell development and regeneration. These findings were confirmed using RNAScope and double label immunohistochemistry with STRC and other taste cell type marker genes. Administration of RANKL, a growth factor required for M cell regeneration led to dramatic upregulation of M cell marker genes in taste papillae from wild type (WT) but not Spib knock out mice. We hypothesize that STRCs and VDCs participate in immune surveillance at the taste papillae in the same manner as M cells, and that perturbances in this pathway might lead to infection, inflammation and taste loss. We will test this hypothesis by thoroughly examining the expression of M cell marker genes in taste papillae using quantitative polymerase chain reaction, RNASeq and histological techniques, and by determining the ability of the RANKL to trigger M cell proliferation in specific pathogen free (SPF) and germ free (GF) WT mice and SPF Spib conditional knockout mice (SpibCKO mice) and taste organoids cultured from them. We will also determine the changes in immune cell recruitment to the taste papillae in all three mouse strains/conditions described above. The ability of STRCs and VDCs in vivo and in taste organoids to transcytose luminal microbes will be measured by quantifying the uptake of fluorescently tagged nanoparticles and green fluorescent protein expressing Escherichia coli. The changes in taste sensitivity in SpibCKO mice will be determined using brief access taste test in a gustometer. Our study represents a novel foray into the intersection between taste biology and immunity and has the potential to deepen the understanding of mucosal immune surveillance at taste papillae. Successful completion of this study promises to help design novel strategies to treat taste loss associated with infection, obesity and aging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $155,500 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Oral Diseases and Disorders Research	000	2	8/7/2023	NON-COMPETING CONTINUATION	$155,500
														Subtotal = $155,500

Issue Date FY: 2022 ( Subtotal = $155,500 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	2200 VINE ST BOX 830861	LINCOLN	NE	68503	LANCASTER	USA	Oral Diseases and Disorders Research	000	1	8/30/2022	NEW	$155,500
														Subtotal = $155,500

Grand Total All Awards = $311,000

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Mucosal Immune Surveillance at the Taste Papillae

Award Number: R03DE032417

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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