Human mucosal-associated invariant T (MAIT) cells are a recently characterized T cell population that is abundant in blood and mucosal tissues including gingival tissue. Importantly, MAIT cells are a unique interface between the immune system and the microbiome due to their ability to recognize bacterial metabolites presented by major histocompatibility complex-related protein 1 (MR1). Once activated, MAIT cells produce pro-inflammatory cytokines and cytotoxic effector molecules, which can lead to clearance of an infection as well as tissue destruction and pathology. Interestingly, inflammatory cytokines are sufficient to activate MAIT cells and induce effector function. This is beneficial in the context of an infection, but is also likely to contribute to immune pathologies. We propose to study how MAIT cell function is altered during peri- mucositis and per-implantitis. The latter is diagnosed when inflammatory factors result in destruction of the supporting bone and tissue ultimately leading to the loss of the dental implant. The overarching goal is to understand if MAIT cells contribute to the inflammatory environment in peri-mucositis and peri-implantitis and how their anti-bacterial properties are altered in these conditions. Defining the role of this novel T cell population, in highly relevant clinical scenarios, is significant because it allows us to understand the interplay of immune system and microbiome and needed to develop future therapeutic intervention strategies.

Public Health Relevance

Human mucosal-associated invariant T (MAIT) cells are located at critical sites of pathogen entry, but their role in the mucosal immune response, specifically in gingival tissue, is poorly understood. So far it has been established that MAIT cell are activated following bacterial infections and eliminate infected cells. Furthermore, inflammatory cytokines alone are sufficient to activate MAIT cells in the absence of bacterial antigen. We propose to define the functional properties of MAIT cells during peri-mucositis and peri-implantitis on a single- cell and population level. Our goal is to provide a thorough definition of MAIT cell function during peri-mucositis and peri-implantitis to understand how inflammation alters MAIT cell function and thus anti-bacterial immunity in gingival tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DE026565-02
Application #
9547364
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Chander, Preethi
Project Start
2017-09-01
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109