Sohil Jayee
Research Mentor(s): Mohammad Farazuddin
Mentor Department: Michigan Nanotechnology Institute for Biology and Medical Sciences
Authors: Sohil Jayee, James R Baker Jr, Mohammad Farazuddin
Session: Session 2 (10:00am – 10:50am)
Presentation Type: Poster 92
Abstract
The human immune system consists of various organs, tissues, and immune cells which work simultaneously to eliminate pathogens. The first barrier, mucosal surfaces, uses key immune cells like dendritic cells (DCs), macrophages, and T cells to coordinate a response and prevent foreign antigens from entering the body. Initially innate immunity activates plasmacytoid DCs and macrophages which engulf pathogens and infected cells to secrete chemoattractants for different inflammatory immune cells. Later, these engulfed pathogens taken up by classical DCs (cDCs) then migrate and present pathogenic peptides through MHC class I and II molecules to T cells and initiate adaptive immunity. Vitamin A, necessary for the development of DCs and their function, significantly influences mucosal immunity. Once DCs metabolize vitamin A into retinoic acid (RA), it regulates functions of other immune cells as well as of DCs. Our lab investigates the role of RA in regulating DC’s function and its effect on adaptive immunity against respiratory viruses. We utilized genetically modified mice expressing a dominant negative form of the retinoic acid receptor a (dnRARa) to disrupt RA signaling in DCs. After infecting dnRARa and control mice with PR8, an influenza virus strain, we analyzed the immune responses at days 3, 6, and 12 post-infection. This allowed us to assess DC populations and T cell activation using flow cytometry and cytokine secretion. The differences in T cell activity between dnRARa and wild-type (control) mice provided insight into RA’s role in priming immune responses. Understanding vitamin A’s role and importance provides information on altering innate and adaptive immunity in opposing respiratory viral pathogens. Furthermore, this information can assist in the development of real-world applications such as nutritional interventions for vitamin A deficient populations, vaccines for respiratory pathogens, and synthetic variants of retinoic acid.
