Chief, Arthritis Section, VA Medical Center
Professor of Medicine
BRBII/III, Suite 757
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: 215-573-2956
Fax: 215-573-7599
E-mail: philipco@mail.med.upenn.edu
Program Summary
Certain mice with genetically impaired apoptosis develop anti-nuclear antibodies and variable expression of lupus like disease. We are interested in the mechanism whereby delayed or aberrant apoptosis contributes to disease and are studying mice with deleted p53 genes and other abnormalities which impair stress-related apoptosis and may serve to provoke autoantibody production. We are also exploring the mechanism of autoimmunity in mice with a deletion in the c-mer protein, which serves to recognize exposed phosphatidylserine residues on dying cells and trigger their phagocytosis.
Program Summary
While SLE autoantibody production is T-cell dependent, the relevant epitopes seen by autoreactive T cells are poorly defined. We have eluted peptides from class II MHC molecules of autoimmune mice and have identified candidate autoantigens. We are studying the immunobiology of these peptide antigens – which T cells are stimulated, and just how these T cells come to provide help for systemic autoantibody production.
1. Behrens EM, Gadue P, Gong S, Garrett S, Stein PL, and Cohen PL. The mer receptor tyrosine kinase: Expression and function suggest a role in innate immunity. Eur J. Immunol 33:2160-7, 2003.
2. Cohen, P.L., et. al..Delayed Apoptotic Cell Clearance and Lupus-like Autoimmunity in Mice Lacking the c-mer Membrane Tyrosine Kinase. J. Exp. Med. (in revision), 2002
3. Suh C, Freed JH, and Cohen PL. T-cell reactivity to MHC class II-bound self peptides in SLE-prone MRL/ lpr mice . J Immunol 170:2229-35, 2003
4. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL , Earp HS, and Matsushima GK. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 6834:207-211, 2001.
