Renal

My laboratory focuses on the molecular and cellular mechanisms of autoimmune disease which are prevalent in women. We are investigating the attack mechanisms instrumental in targeted tissues for autoimmune destruction, and probing for the barriers that protect these tissues from autodestruction. Our penultimate goal is to identify the cells and molecules instrumental in inciting and promoting autoimmune tissue damage. The final goal is to construct a therapeutic strategy to block autoimmune tissue destruction. Our studies have concentrated on autoimmune kidney and pancreatic islet cell injury. Initially, we determine the pathologic invading cells prior to injury and identify the candidate molecules responsible for the recruitment and survival of these cells. To establish whether a candidate molecule fosters or thwarts tissue injury we introduce the candidate molecule into the tissue using genetic approaches. In addition, we use transgenic and gene "knock-out" strategies to test the importance of a selected molecule in the autodestructive process. Once we establish that the candidate molecule is instrumental in the pathogenesis, we identify the cells that produce this candidate molecule and determine the regulation of its receptor. Our future goals include local gene transfer of molecules that block the receptors of molecules instrumental in autoimmune tissue destruction.

In addition, we have projects defining the molecular defects in the macrophage that are pivotal in autoimmune disease.

The current projects include chemokines as therapeutic targets for Lupus, Novel co-stimulatory pathways in lupus, IL-15 a survival factor for epithelial cells, the role of IL-12 and IL-15 in autoimmune kidney disease, macrophage growth factors in inflammatory and autoimmune kidney disease.

Recent Publications:

1. Tesch GH, Schwarting A, Kinoshita K,Lan HY Rollins BJ, Kelley VR. MCP-1 promotes macrophage-mediated tubular, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest 1999;103:73-80.
   
   
2. Schwarting A, Tesch G. Kinoshita K, Maron R, Weiner HL, Kelley VR. IL-12 drives IFN-g dependent autoimmune kidney disease in MRL-Faslpr mice. J Immunol 1999; 163: 6884-6891.
   
   
3. Tesch GH, Maifert S, Schwarting A, Rollins BJ, Kelley VR. MCP-1 dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Faslpr mice. J Exp Med 1999;190:1813-1824.
   
   
4. Kinoshita K, Tesch, G, Schwarting A, Maron R, Sharpe AH, Kelley VR. Costimulation by B7-1 and B7-2 Is Required for Autoimmune Disease in MRL-Faslpr Mice. J Immunol 2000; 164:6046-6056.
   
   
5. Wada T, Schwarting A, Chestnutt MS, Wofsy D, Kelley VR. Nephritogenic cytokines and disease in MRL-Faslpr kidneys are dependent on multiple T cell subsets. Kidney Int 2001;59:565-578.
   
   
6. Shinozaki M, Hirahashi J, Lebedeva T, Liew FY, Salant DJ, Maron R, Kelley VR. IL-15, a survival factor for kidney epithelial cells , counteracts apoptosis and inflammation during nephritis. J. Clin Invest 2002;109:951-960.
   
   
7. Lenda DM, Kikawada E, Stanley ER, Kelley VR. CSF-1 dependent macrophage proliferation , and activation results in tubular apoptosis during renal inflammation. J Immunol 2003;170:3254-3262.
   
   
8. Kikawada E, Lenda DM, Kelley VR. IL-12 deficiency in MRL-Faslpr mice: Delays nephritis and intrarenal IFN-y production, and reduces systemic pathology. J Immunol 2003;170:3915-3925.
   
   
9. Lenda DM, Stanley ER, Kelley VR. Negative role of colony stimulating factor-1 in macrophage, T and B Cell mediated autoimmune disease in MRL-Faslpr mice. J Immunol 2004;173:4744-4754.