In the world of immunology, the gut is garnering new respect. Cayla Rodia, a doctoral student in the Department of Nutritional Sciences, is fascinated with the intestine’s involvement with the immune system.
“I love the intestine and I really think it is the most underrated organ,” Rodia says. “People used to think it was simply for digestion, but we’re learning it has so many interconnected abilities. Seventy percent of the immune system is in the gut.”
“The gut immune system is in constant contact with potential antigens,” she continues. “That system has to be working correctly to prevent inflammatory or immune responses elsewhere.”
Rodia is studying apolipoprotein C-III (apoC-III) and its effect on the immune system. ApoC-III is a protein that is carried by lipoproteins from the intestine into the circulatory system. During this process, there is an unknown interaction in the gut with the immune system as that lipoprotein goes into circulation.
ApoC-III plays a role in increasing blood plasma lipid levels, so elevated apoC-III is considered a risk for cardiovascular disease (CVD). ApoC-III directly inhibits the uptake of lipoproteins into tissue, sending more into circulation, which can lead to inflammation. With this link to CVD in mind, Rodia conducted controlled studies in mice and found that apoC-III in the intestine is beneficial to the immune response.
“I started this project by looking at the Western diet and its effects on the gut immune system, and that led me to look at inflammatory bowel disease (IBD),” she says. “During this study, we’ve actually found that apoC-III protects our mice from IBD. So, while I found this beneficial effect of apoC-III in the intestine, we still have this knowledge that apoC-III is really detrimental in circulation.”
“We don’t see dietary fat as regulating apoC-III,” Rodia says. “We don’t know what regulates it within the intestine but in humans, we think it is a genetic factor. There are some mutations in people that cause them to have less apoC-III. I’m thinking there was some kind of evolutionary benefit to having apoC-III to get you into maturity, but as a population, we have shifted our diet and exercise patterns so we are now prone to chronic diseases, and it seems that the extra apoC-III is having this negative cardiovascular effect.”
Rodia is further studying the positive effects of apoC-III on the gut immune system, while trying to figure out these two opposing effects.
“One important factor to consider is that a medication is currently being developed to decrease apoC-III,” Rodia points out. “I think before people utilize a prescription intervention, it is critical to find out if this could have detrimental side effects, especially in the gut immune system.”
While she’s made a lot of progress, Rodia is still piecing the parts together. “I’ve observed this specific phenotype in mice that overexpress apoC-III, and I’ve seen the opposite phenotype in mice lacking apoC-III. Based on previous literature, it appears that too little apoC-III is associated with increased risk of IBD, and too much may increase the risk of CVD. The physiology is there in our mice. I’m trying to figure out the mechanism. Why is this happening in the intestine and why is something different happening in circulation? We really don’t know that yet. I feel like I have a lot of questions to answer.”
Rodia plans to complete her doctorate in the spring of 2019 and is considering a postdoc in immunology, followed by a career in research.
Alison Kohan, assistant professor of molecular nutrition, is Rodia’s faculty advisor. “I believe Cayla’s research will make a significant contribution to the field,” Kohan says. “Cayla is clear, concise, well organized and has complete ownership of her research questions. Cayla’s research fills a gap in our knowledge of how the intestine and immune system interact to drive cardiovascular inflammation.”
Rodia was selected to present at the Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) division of the American Heart Association Conference, held in Minneapolis in May 2017. She received the 2017 ATVB Travel Award for Young Investigators for her presentation, “ApoC-III promotes anti-inflammatory Treg phenotype through modulation of intestinal dendritic cell activation.”
“Cayla is only two-and-a-half years into her Ph.D. program, and it is obvious that she is exceptionally bright, critical and extremely self-motivated,” Kohan says. “She is working on something that is totally new for the field. She and I have learned immunology side-by-side.”
“I’ve gained a sense of scientific freedom working in the Kohan lab,” Rodia says. “I’m blessed to be able to pursue my own ideas. Dr. Kohan is great at fostering curiosity. And there is a huge sense of community in the Nutritional Sciences Department. It has been really helpful to be able to talk to the other advisors and ask questions about our research. We also have a link with UConn Health. I’ve run some of my data samples at the Health Center, and I’ve found it beneficial to be able to speak with some of the advisors there and build that relationship.”
“I really enjoy the immunology portion of my project,” Rodia says. “There is a rising field of nutritional immunology that really interests me. I want to stay in research. I really like the freedom to be curious and ask questions. That’s an important part of science.”