Immune System Heroes
Banding Together to Bring Relief to Gulf War Veterans:
In the years following the first Gulf War (1990–91), veterans reported chronic medical conditions that included fatigue, frequent or persistent headache, and frequent or persistent muscle or joint pain. Gastrointestinal symptoms were also in the mix, and the search for answers and treatments for those ailments includes collaboration between RFU researcher Joseph Reynolds, PhD, and a gastroenterology team at the Captain James A. Lovell Federal Health Care Center.
Though he began as a chemist in his undergraduate work, an elective in immunology changed everything for Joseph Reynolds, PhD. He described how immunology revealed the ways the body protects and defends itself against uncountable threats: “The immune system is so fascinating, like something out of a comic book — so many cells doing so many amazing things, and the public has no idea how many threats these cells are fighting off for them constantly.” At the encouragement of his mentors, Dr. Reynolds took his newfound fascination with the immune system’s heroics and dove into a life in discovery.
Always Looking Closer
Dr. Reynolds’ work at RFU has two main focuses. His NIH R01 grant examines T-cells and how they mediate autoimmune responses in multiple sclerosis, but his research also branches into the study of cytokines. “My lab started to look closer at models of inflammation and became interested in interleukin 17-C, which is found in the intestinal epithelial cells,” he said. “Using animal models, we found that it was very protective against inflammatory bowel disease.”
While studying this model, Dr. Reynolds found a novel research opportunity in partnership with the Captain James A. Lovell Federal Health Care Center (FHCC), working closely with Axel Feller, MD, the former chief of gastroenterology. This collaboration forged new research tracks while addressing the needs of veterans with long-standing repercussions from their service in the Gulf War.
“Dr. Feller often lamented that the FHCC sees many active duty soldiers with irritable bowel syndrome, particularly Gulf War veterans,” he said. “In sharing ideas, I mentioned my mouse models, and they offered a pilot program specifically studying these veterans. We took the concept of the cytokine interleukin 17-C being gut protective and found that it helped the epithelial barrier repair itself.”
The study also garnered significant findings around the effects of neurotoxins, another dark consequence of the Gulf War. “It’s hard to prove 30 years later, but one of the major factors involves exposure to low-dose nerve agents, including Sarin gas. If that hypothesis is true, we should be able to see some effects of nerve agent exposure, what it does to the gut, and how our cytokine family fits into that web.
“To study this, we started using DFP (a surrogate for Sarin, 40 times less toxic but using a similar mechanism). Our initial hypothesis turned out to be entirely correct. It did enormous damage to the gut: pipe junctions, control, permeability are all really dysregulated, causing a leaky gut-type syndrome. The composition of the microbiome is completely altered,” he added. “This was particularly fascinating because most work in this field focuses on neuroinflammation — we were the first to show that it affects the gut significantly, too. Fortunately, our studies also showed that the cytokine was very protective. If you pre-dose the cells or use it as a treatment, you can improve the damage or lessen the effects of the exposure.”
Assembling a Team
In the summer of 2022, Dr. Reynolds shared some of these findings in a presentation titled “Modeling Organophosphate Exposure and Gastrointestinal Dysfunction in a Model of Gulf War Illness” as part of the U.S. Department of Veterans Affairs National VA Research Week, a celebration of a successful research partnership.
“In the modern world of science, with so much that can be done digitally, I feel like you have no excuse for at least trying to improve your lab and your program by reaching out.”
In the midst of his research, Dr. Reynolds wears many hats at Rosalind Franklin University, serving as the director of the Center for Cancer Cell Biology, Immunology, and Infection; the graduate program administrator for microbiology and immunology; and as a primary mentor for students within the discipline. In training students to form similar collaborative research partnerships, Dr. Reynolds emphasizes the importance of reaching out and listening well. “In the modern world of science, with so much that can be done digitally, I feel like you have no excuse for at least trying to improve your lab and your program by reaching out. If I identify a deficiency in my research, I actively seek to plug that gap and learn from others.”
Looking back at the course of his own growth in science, Dr. Reynolds was struck by the generosity of his mentors and he now mentors students of his own.
“Something I’ve come to appreciate much more over the years is the time that my previous mentors spent educating, training and encouraging me. I didn’t realize how much I’d enjoy passing that legacy on until I started mentoring students of my own.”
Joseph DiMario, PhD, dean of SGPS, highlights what an asset Dr. Reynolds is to SGPS students: “The School of Graduate and Postdoctoral Studies is deeply grateful to have a dedicated mentor, researcher, collaborator and colleague in Dr. Joseph Reynolds.” In his ongoing research, Dr. Reynolds continues to shine a light on the heroism of the immune system and support the heroic efforts of the next generation of scientists.
Aubrey Penney is academic program coordinator for RFU’s School of Graduate and Postdoctoral Studies.