 |
William J. Karpus, PhDProfessor
|
To visit the Karpus lab website click here.
The central theme of my research program is the role of chemokines and chemokine receptors in the regulation of autoimmune disease, chronic viral diseases, mucosal immunity and tolerance to gut pathogens. The three major research projects are listed below.
1. We study the pathogenesis and regulation of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). EAE follows a relapsing-remitting course of paralysis and is characterized by lymphocyte and monocyte infiltrates of the central nervous system (CNS) with areas of demyelination. It is clear that similarities exist in both clinical course and histopathology between relapsing forms of EAE and MS and this allows us to develop new therapeutic strategies for human disease. As a result of this autoimmunity, T lymphocytes migrate from the peripheral lymphoid tissue and blood to the brain and spinal cord. This is a central feature in the pathogenesis of both MS and EAE. A number of factors, including cell-associated integrins and soluble chemokines, regulate the migration or trafficking of T cells to tissue sites. We have identified a number of chemokines and chemokine receptors responsible for paralytic disease induction and progression. Current projects include:
a. Chemokine regulation of dendritic cell trafficking in EAE development, remission and relapse.
b. Chemokine regulation of T cell effector function.
c. Chemokine regulation of T cell trafficking during remission and disease relapses.
d. Targeting of chemokines for novel therapeutic intervention.
e. Epitope spreading and lymphocyte trafficking.
2. Theiler’s murine encephalomyelitis virus (TMEV) chronically infects mice and induces a progressive paralytic disease resembling MS. In contrast to EAE, the disease course is chronic progressive and un-remitting. However, lymphocytes and monocytes infiltrate the brain and spinal cord and induce demyelination. We have identified chemokines, MCP-1 in particular, responsible for the induction of paralytic disease. Current projects include:
a. Chemokine receptor regulation of chronic disease progression.
b. Chemokine regulation of resultant autoimmune responses.
c. Chemokine regulation of viral persistence.
3. There is a growing body of evidence that indicates aberrant chemokine receptor expression by both human B cell and T cell lymphomas and leukemias. Similarly, chemokine ligand expression as been noted in human B cell, T cell, and Hodgkin’s lymphoma. These findings raise the possibility that chemokines and their receptors may be involved in lymphoma cell movement between lymphoid as well as non-lymphoid sites. The idea that chemokines and their receptors functionally direct the migration of lymphoma cells to lymphoid and extra-lymphoid tissues has not been formally tested either clinically or preclinically. Using a mouse model of B cell lymphoma we propose to test the hypothesis that chemokine expression in lymphoid and non-lymphoid tissue regulates the migration of lymphoma cells expressing specific chemokine receptors to those particular tissues.
Karpus, W.J., K.J. Kennedy, B.T. Fife, J.L. Bennett, M.C. Dal Canto, S.L. Kunkel, and N.W. Lukacs. Anti-CCL2 treatment inhibits Theiler’s murine encephalomyelitis virus induced demyelinating disease. J. NeuroVirol. 12: 1-11, 2006.
DePaolo, R.W., R. Lathan, B.J. Rollins, and W.J. Karpus. The Chemokine CCL2 Is Required for Control of Murine Gastric Salmonella enterica Infection. Infection and Immunity 73: 6514-6522, 2005.
Elhofy, A., J. Wang, M. Tani, B.T. Fife, K.J. Kennedy, J. Bennett, D. Huang, R.M. Ransohoff, and W.J. Karpus. Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis. J. Leukoc. Biol. 77: 229–237, 2005.
Carpentier, P.A., W.S. Begolka, J.K. Olson, A. Elhofy, W.J. Karpus, and S.D. Miller. Differential Activation of Astrocytes by Innate and Adaptive Immune Stimuli. Glia 49:360–374, 2005.
DePaolo, R.W., R. Lathan, and W.J. Karpus. CCR5 Regulates High Dose Oral Tolerance by Modulating CC Chemokine Ligand 2 Levels in the GALT. J. Immunol. 173: 314–320, 2004.
DePaolo, R.W., B.J. Rollins, W. Kuziel, and W.J. Karpus. High dose oral tolerance is dependent on the chemokine CCL2 and its receptor CCR2. J. Immunol. 171: 3560-3567, 2003.
Bennett, J.L., A. Elhofy, M.C. Dal Canto, M. Tani, R.M. Ransohoff, and W.J. Karpus. CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45highCD11b+ monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease. J. NeuroVirol. 9:623-636, 2003.
Fife, B.T., M. Paniagua, N.W. Lukacs, S.L. Kunkel, and W.J. Karpus. Selective CCR1 expression by central nervous system-infiltrating encephalitogenic T cells during experimental autoimmune encephalomyelitis. J.Neurosci. Res. 166: 7617-7624, 2001.
Fife, B.T., K.J. Kennedy, M. Paniagua, N.W. Lukacs, S.L. Kunkel, A. D. Luster, and W.J. Karpus. CXCL10 (IFN-g-inducible protein 10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis. J. Immunol. 166: 7617-7624, 2001.
Fife, B.T., G. Huffnagle, W. Kuziel, and W.J. Karpus. CC chemokine receptor 2 is critical for the induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 192: 899-906, 2000.
 |
View Publications by Bill Karpus listed in the National Library of Medicine (PubMed). |
Go to Faculty Index |
Go to IGP Home Page |