Massachusetts General Hospital (MGH) investigators have identified an inflammatory molecule that appears to play an essential role in the autoimmune disorder systemic lupus erythematosus (SLE), commonly known as lupus. In their report, which was published online on April 6, 2015 in Nature Immunology, the researchers describe finding that a protein that regulates certain cells in the innate immune system - the body's first line of defense against infection - activates a molecular pathway known to be associated with lupus and that the protein's activity is required for the development of lupus symptoms in a mouse model of the disease. "This study is the first demonstration that the receptor TREML4 amplifies the cellular responses transmitted through the TLR7 receptor (toll-like receotor 7) and that a lack of such amplification prevents the inflammatory overactivation underlying lupus," says Terry Means, Ph.D., of the Center for Immunology and Inflammatory Diseases in the MGH Division of Rheumatology, Allergy, and Immunology. "Our preliminary results suggest that TREML4-regulated signaling through TLR7 may be a potential drug target to limit inflammation and the development of autoimmunity." Lupus is an autoimmune disorder characterized by periodic inflammation of joints, connective tissues, and organs, including heart, lungs, kidneys, and brain. TLR7 is one of a family of receptors present on innate immune cells like macrophages that have been linked to chronic inflammation and autoimmunity. Animal studies have suggested that overactivation of TLR7 plays a role in lupus, and a gene variant that increases expression of the receptor has been associated with increased lupus risk in human patients. The current study was designed to identify genes for other molecules required for TLR7-mediated immune cell activation.Login Or Register To Read Full Story