2008 Genetics, Human Lupus Biology
Signaling of proteins called interferons, which are produced by cells of the immune system in response to foreign substances such as viruses and parasites, is increasingly recognized as important to the cause and development of lupus.
Dr. Chan hypothesizes that certain genetic material responsible for regulating approximately 30 percent of the human genome—very small “microRNA molecules”—participate in controlling the activity and signaling of these interferons.
With LRI funding, Dr. Chan’s team will investigate which of the microRNAs might be involved, applying an analysis of microRNAs already completed on a small number of people to a much larger cohort.
If his findings are positive, the team will attempt to determine whether the microRNAs identified actually affect interferon signaling pathways—and play a role in lupus.
They found that the microRNA, Toll-like receptor TLR2, can switch itself off to protect the body from inflammation. Published in the Journal of Immunology, these results provide insights into how Toll-like receptor proteins can be targeted in developing new treatments for lupus.
Regulation of TLR2-mediated tolerance and cross-tolerance through IRAK4 modulation by miR-132 and miR-212. Nahid MA, Yao B, Dominguez-Gutierrez PR, Kesavalu L, Satoh M, Chan EK. J Immunol. 2013 Feb 1;190(3):1250-63. doi: 10.4049/jimmunol.1103060. Epub 2012 Dec 21.