An intrinsic complement-NLRP3 axis regulates human TH1 responses. T cell receptor activation and CD46 costimulation trigger NLRP3 expression and intracellular C5a generation. Subsequent intracellular C5aR1 engagement induces ROS production (and possibly IL1B gene transcription) and NLRP3 assembly, which in turn mediates IL-1β maturation. Autocrine IL-1β promotes TH1 induction (IFN-γ production) but restricts TH1 contraction (IL-10 coexpression). C5aR2 cell surface activation by secreted C5a negatively controls these events via undefined mechanisms. Dysfunction of this system contributes to impaired TH1 responses in infection or increased TH17 responses during intestinal inflammation.
Researchers have unlocked secrets of our ancient immune system. An international team, including researchers from The University of Queensland, identified interactions between immune system pathways which could improve the treatment of diseases such as inflammatory bowel disease (IBD), which affects millions of people worldwide. The immune system has an adaptive immune system, which produces antibodies against an infection, and a very ancient pathway, the innate immune system ~”… 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,” Professor Cooper said.
“Researchers always thought key components of these pathways acted alone, but our teams have discovered they can communicate and work together.” The discovery may have significant implications for treating a range of autoimmune and inflammatory diseases. Arbore et al showed innate and adaptive immunity converge in human and mouse T cells. Activated T cells express components of the complement cascade, which in turn leads to the assembly of NLRP3 inflammasomes—both critical components of innate immunity that help hosts detect and eliminate microbes. In T cells, complement and inflammasomes work together to push T cells to differentiate into a specialized subset of T cells important for eliminating intracellular bacteria.
“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.” Professor Cooper and the international team have developed 2 small molecules that each block one pathway. “We have tested these molecules and the results show that they both reduce inflammation when administered separately,” he 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.” http://www.eurekalert.org/pub_releases/2016-06/uoq-uso061516.php http://science.sciencemag.org/content/352/6292/aad1210
Recent Comments