The focus of these studies is to define the role of dendritic cells in ocular-associated mucosal immune responses in order to achieve the long-term objective of developing novel, clinically relevant immunization strategies to protect the external ocular compartment. The hypotheses to be tested are: 1. antigen uptake and delivery to ocular-related lymphoid inductive sites is mediated by dendritic cells and potentiated by factors that activate the dendritic cell maturation program; 2. dendritic cell targeted immunomodulators determine the strength and outcome of ocular mucosal immune responses; and 3. dendritic cells play a role in the effector stage of ocular mucosal immune responses. These hypotheses will be tested by pursuing the following Specific Aims:
AIM 1. To define conditions that enhance antigen localization in ocular-related mucosal inductive sites.
This aim will phenotypically identify cell types involved in antigen uptake from the ocular or nasal surface and translocation to nasal associated or cervical lymphoid tissues following ocular-topical or intranasal immunization as well as investigate dendritic cell (DC)-targeted strategies to enhance antigen uptake and translocation to lymphoid inductive sites.
AIM 2. To determine the role of dendritic cells in the inductive phase of ocular immune responses.
This aim will utilize an in vitro system to assay DC maturation and polarization, develop in vivo mucosal immunization protocols to activate DC maturation and polarization programs for enhanced tear IgA and systemic IgG antibody responses and investigate the involvement of plasmacytoid DC in ocular immune responses.
AIM 3. To investigate the role of dendritic cells in the effector stage of ocular immune responses.
This aim will utilize dendritic cell targeted immunization protocols to investigate the presence of lacrimal gland dendritic cell populations during ocular effector responses, mechanisms facilitating dendritic cell recruitment to lacrimal gland and functions of lacrimal gland dendritic cells. It is expected that a detailed understanding of the role of dendritic cells in the inductive and effector phases of ocular-associated mucosal immune responses will provide information essential to the development of new, clinically relevant vaccination strategies that will optimize protection of the ocular surface.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VISA (01))
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Shen, Grace L
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Wayne State University
Schools of Medicine
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Gill, Randall F; Pirockinaite, Gaila; O'Sullivan, Nancy L et al. (2010) Nasal-associated lymphoid tissue is not an absolute requirement for the induction of rat tear IgA antibody responses. Curr Eye Res 35:1-8
O'Sullivan, Nancy L; Baylor 3rd, Alfred E; Montgomery, Paul C (2007) Development of immortalized rat conjunctival epithelial cell lines: an in vitro model to examine transepithelial antigen delivery. Exp Eye Res 84:323-31