2006 General Immune System Function
With LRI funding, Dr. Greidinger aimed to find better ways to predict which organs and tissues in a person with lupus are at imminent risk for attack.
Within two years of winning LRI funding, he has in fact had success in developing a special model to assess the potential of immune system “danger signal” sensors to do just this. He now has extended funding from the Veterans Administration.
To determine the mechanisms involved in this targeting of organs, he used a novel model that his laboratory developed in which different organs are singled out based on the activation of components of the innate immune system—the sensors of “danger signals” that prompt the immune system to swing into action.
In the time remaining on his LRI grant, he aims to leverage his other innovative ideas on the mechanisms of selective tissue targeting in autoimmunity into additional federal grant support.
Dr. Greidinger’s findings have the potential to lead to novel therapies that can convert severe disease into milder disease.
Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Bernard JJ, Cowing-Zitron C, Nakatsuji T, Muto J, Borkowski AW, Martinez L, Greidinger EL, Yu BD, Gallo BL. Nature Medicine 18, 1286–1290 (2012).
Tissue targeting of anti-RNP autoimmunity: Effects of T cells and myeloid dendritic cells in a murine model. Greidinger EL, Zang Y, Fernandez I, Berho M, Nassiri M, Martinez L, Hoffman RW. Arthritis Rheum. 2009 Jan 29;60(2):534-542.
CD4+ T cells target epitopes residing within the RNA-binding domain of the U1-70-kDa small nuclear ribonucleoprotein autoantigen and have restricted TCR diversity in an HLA-DR4-transgenic murine model of mixed connective tissue disease. Greidinger EL, Zang YJ, Jaimes K, Martinez L, Nassiri M, Hoffman RW. J Immunol. 2008 Jun 15;180(12):8444-54.
Differential tissue targeting of autoimmunity manifestations by autoantigen-associated Y RNAs. Greidinger EL, Zang Y, Martinez L, Jaimes K, Nassiri M, Bejarano P, Barber GN, Hoffman RW. Arthritis Rheum. 2007 May;56(5):1589-97.
In 2008, Dr. Greidinger won a $650,000 grant from the Veterans Administration to further study immune response patterns and assessing their potential for generating new therapies that could convert severe disease to mild disease.