Nicholas Litsas
Pronouns: HeHim
Research Mentor(s): Mohammad Farazuddin
Research Mentor School/College/Department: Michigan Nanotechnology Institute for Biology and Medical Sciences / Medicine
Program: UROPF
Session: Session 2 (10:00am – 10:50am)
Authors: Nicholas Litsas, James Baker Jr, Mohammad Farazuddin
Abstract
Retinoic acid (RA) is a metabolite of vitamin A that regulates functions of many immune cells helping maintain the body’s mucosal immunity. It is critical for the production of Immunoglobulin-A, the most abundant antibody in the body that is found in mucous membranes lining the intestine and the respiratory tract. It also induces migration of T lymphocytes as well as dendritic cells (DC) to mucosal surfaces. Although macrophages and B-lymphocytes can convert vitamin-A into retinoic acid, it is DCs that are the main metabolizers. For this reason, we aimed to investigate the role of RA signaling in the DC’s function. The role of DCs in the immune system is to present antigens to T lymphocytes, the beginning of the adaptive immune response, that leads to the production of specific antibodies that target the matching pathogen. In order to analyze the effects of RA on this function, we cultured DCs from retinoic acid receptor ? (RAR) knockout mice. This allows us to compare the function between the normal wildtype cells and the cells expressing the nonfunctional retinoic acid receptor. We stimulated the DC with 3p-hp (5’ triphosphate hairpin RNA), an in vitro synthesized negative strand of influenza A and increasing concentration of RA in the culture media. Post incubation, DC RNA was extracted and cDNA synthesis was performed. We used qPCR and measured the gene expression of IFN-?, IL1-? IL6, IL12, TNF-?? and ?-actin(house-keeping gene). ELISA was also used to quantify total cytokine production. The knockout cells showed a decrease in IL1-?, IL6, and IL12 but an increase in IFN-? and TNF-?? when compared to the wild-type cells. This conclusion will help determine the role of retinoic acid on the dendritic cell’s function following bacterial or viral infection. Studying the changes in interferons and proinflammatory cytokines expression in the absence of RA, will help us understand the impact of vitamin A on DC behavior following virus infection.
