autoimmunity • systemic lupus erythematosus • autoantibodies • T cells • cell death
My research focuses on systemic lupus erythematosus (SLE), which is an autoimmune disease affecting approximately one in every 1000 Canadian women, and often causing chronic pain and premature death. Individuals with SLE develop an immune response against their own cells, but it is unclear why this response develops. We hypothesize that cells in SLE-prone individuals die in a manner that causes them to appear foreign, thus resulting in an immune response to these cells. We will use an induced model of SLE to determine whether injecting cells that have died in different ways can produce SLE autoantibodies in mice. We will also evaluate whether inhibiting different types of cell death in mice that develop SLE-like disease spontaneously can prevent autoantibody production and disease. Our research will identify the role of different forms of cell death in the development of SLE, and how modifying cell death may produce or prevent SLE.
Dieudé, M., Correa, J.A., Neville, C., Pineau, C., Levine, J.S., Subang, R., Landolt-Marticorena, C., Su, J., Kassis, J., Solymoss, S., Fortin, P.R., and Rauch, J. Autoantibodies to heat shock protein 60 are associated with arterial vascular events in patients with anti-phospholipid antibodies. Arthritis Rheum. 63: 2416-2424, 2011.PMID: 21506099.
Laplante, P., Amireault, P., Subang, R., Dieudé, M., Levine, J.S., and Rauch, J. Interaction of &beta2-glycoprotein I with lipopolysaccharide leads to toll-like receptor 4 (TLR4)-dependent activation of macrophages. J. Biol. Chem. 286: 42494–42503, 2011. PMID: 21965665.
Patel, V.A., Feng, L., Lee, D.J., Massenberg, D., Pattabiraman, G., Antoni, A., Schwartz, J.H., Lieberthal, W., Rauch, J., Ucker, D.S., and Levine, J.S. Recognition-dependent signaling events in response to apoptotic targets inhibit epithelial cell viability by multiple mechanisms: implications for non-immune tissue homeostasis. J. Biol. Chem. 287: 13761–13777, 2012. PMID: 22396534.
Levine, J.S., Subang, R., Setty, S., Cabrera, J., Laplante, P., Fritzler, M., and Rauch, J. Phospholipid-binding proteins differ in their capacity to induce autoantibodies and murine systemic lupus erythematosus. Lupus 23: 752-768, 2014. PMID: 24695867.
Salem, D., Subang, R., Okazaki, Y., Laplante, P., Levine, J.S., Kuwana, M., and Rauch, J. &beta2-glycoprotein I-specific T cells are associated with epitope spread to lupus-related autoantibodies. J. Biol. Chem. 290: 5543-5555, 2015. PMID: 25555913.