Project: Research project

Project Details


DESCRIPTION (Adapted from applicant's abstract): The oral cavity is a "portal
of entry" for bacteria, fungi and other infectious agents that reach the
respiratory and gastrointestinal tracts. Lining these tracts is the MALT,
which can induce immunity or oral tolerance against bacteria species. The
antigen-presenting cells known as DCs form a discrete microanatomical
organization with T cells in MALT Peyer's patch, which is crucial for
initiation and regulation of the immune response. Work from our laboratory
and others have established the human oral mucosa as a rich repository of DCs.
We presently understand little about the function and organization of DCs in
these tissues. This R21 application proposes the hypothesis that, if proven,
will support a new paradigm - that adaptive immunity is regulated at several
levels by: (1) distinct DCs subsets that infiltrate the oral mucosa; (2) TLRs
expressed; and (3) the antigens encountered. Our overall hypothesis is that
the human oral mucosal DCs play pivotal roles in regulation of the adaptive
immune response to specific antigens. The sub-hypotheses are: (1) distinct
DC subsets infiltrate different microanatomical sites in the gingival/buccal
mucosa; (2) these DC subsets are differentially responsive to LPS and other
antigens by virtue of the expression of antigen-selective TLR2 and TLR4; and
(3) the T cell response to antigens is regulated by DC responsiveness. The
present application proposes the following aims: Aim 1: To characterize the DC
subsets that infiltrate human oral mucosa in health and disease; and Aim 2: To
determine the ability of DC subsets to regulate the T cell response to
antigens in vitro. The PI has assembled a team of investigators with
expertise in microbiology, oral pathology/stomatology, immuunohistochemistry,
LPS purification/characterization, DC/Langerhans cell function and T cell
function to carry out these studies. The investigators are all located on the
Dallas campus of the Baylor Medical Center Hospital, including Baylor College
of Dentistry-TAMUS and the Baylor Institute for Immunology Research. It is
hoped this research will advance our understanding of how adaptive immunity to
microbial antigens is initiated and regulated at the mucosal level. Our
short-term objective is to acquire sufficient preliminary data/publications to
facilitate the successful submission of an R01 proposal(s). Our long-term
objective is to develop this research to the level of a program project on DCs
and the mucosal immune response.
StatusNot started


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