Evidence supporting the vital role the innate immune system has among inflammatory diseases continues to grow. Now, an international team of researchers believes they have unlocked secrets of the ancient immune system, a significant scientific advance that could help scientists and clinicians in the global fight against disease. The research team identified interactions between immune system pathways that could improve the treatment of diseases such as inflammatory bowel disease (IBD), which affects millions of people worldwide.
The human immune system is comprised of two parts: the adaptive immune system, which produces antibodies against an infection, and a very ancient pathway, known as the innate immune system.
“Innate immunity is so old it goes all the way down to frogs, fish, and even insects,” explained study co-author Matt Cooper, Ph.D., professor at the University of Queensland’s Institute for Molecular Bioscience (IMB). “It stops us getting infections, but it also drives a lot of inflammatory diseases. So, in one case it's keeping us alive by stopping the bugs getting us, but if it goes wrong, we start to get diseases like arthritis, multiple sclerosis, and IBDs, such as colitis.”
In the traditional understanding of immune activation, innate immune cells—macrophages and dendritic cells—recognize invading microbes and then alert adaptive immune cells—T cells—to respond.
“Researchers always thought key components of these pathways acted alone, but our teams have discovered they can communicate and work together,” Dr. Cooper noted.
This new research may have significant implications for treating a range of autoimmune and inflammatory diseases. The findings from this study were published recently in Science in an article entitled “T Helper 1 Immunity Requires Complement-Driven NLRP3 Inflammasome Activity in CD4+ T Cells.”
“Inflammation in diseases such as colitis occurs when the immune system is activated inappropriately and causes symptoms, including pain, diarrhea, fever, and weight loss,” Dr. Cooper remarked. “Current treatments are not always effective, possibly because they are only blocking one of the key pathways and inflammation still occurs through the other pathway.”
The research team examined whether innate immune system proteins—NLRP3 in particular—could activate CD4+ T cells, which are part of the adaptive immune pathway.
“Our results demonstrate that the regulated cross-talk between intracellularly activated complement components (the “complosome”) and the NLRP3 inflammasome is fundamental to human TH1 induction and regulation,” the authors wrote. “The finding that established innate immune pathways are also operative in adaptive immune cells and orchestrate immunological responses contributes to our understanding of immunobiology and immune system evolution.”
Additionally, during their search to understand the role of innate immunity in inflammatory disease better, the researchers discovered two small molecule inhibitors—one for each immune system pathway.
“We have tested these molecules, and the results show that they both reduce inflammation when administered separately,” Dr. Cooper said. “This work is still in the early stages, but we are hopeful our ongoing research will lead to more effective treatments for the millions of IBD sufferers.”