About

William J. Karpus is a Professor and Dean of the Graduate School at the Department of Pathology and Laboratory Medicine at the University of Wisconsin–Madison. His research focuses on the role of chemokines in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). He employs this model system to understand leukocyte migration in the pathogenesis of demyelinating diseases. His work has identified key chemokines and receptors involved in leukocyte migration and function through various approaches, including neutralizing antibody treatment and genetically modified mice. These studies have highlighted significant roles for specific chemokines and chemokine receptors in EAE pathogenesis and suggest these factors as potential therapeutic targets for MS. Additionally, he has demonstrated the involvement of Delta Like Ligand-mediated Notch signaling in regulating chemokine receptor surface expression, which controls T cell migration to the central nervous system. Currently, he is not accepting new students or postdoctoral fellows.

Research topics

• Biology
• Immunology
• Chemistry
• Internal medicine
• Medicine
• Neuroscience
• Pathology
• Anatomy

Selected publications

• Experimental Autoimmune Encephalomyelitis in the Mouse

  Current Protocols · 2021 · 20 citations

  Senior authorCorresponding
  • Immunology
  • Biology
  • Chemistry

  This article details the materials and methods required for both active induction and adoptive transfer of experimental autoimmune encephalomyelitis (EAE) in the SJL mouse strain using intact proteins or peptides from the two major myelin proteins: proteolipid protein (PLP) and myelin basic protein (MBP). Additionally, active induction of EAE in the C57BL/6 strain using myelin oligodendrocyte glycoprotein (MOG) peptide is also discussed. Detailed materials and methods required for the purification of both PLP and MBP are described, and a protocol for isolating CNS-infiltrating lymphocytes in EAE mice is included. Modifications of the specified protocols may be necessary for efficient induction of active or adoptive EAE in other mouse strains. © 2021 Wiley Periodicals LLC. Basic Protocol: Active induction of EAE with PLP, MBP, and MOG protein or peptide Alternate Protocol: Adoptive induction of EAE with PLP-, MBP-, or MOG-specific lymphocytes Support Protocol 1: Purification of proteolipid protein Support Protocol 2: Purification of myelin basic protein Support Protocol 3: Isolation of CNS-infiltrating lymphocytes.

  PublisherDOI

• CNS lymphangiogenesis regulates fluid homeostasis and immunity during neuroinflammation

  The Journal of Immunology · 2020

  • Pathology
  • Anatomy
  • Medicine

  Abstract Recent reports have described meningeal lymphatic vessels residing in the dural layer surrounding the dorsal and basal regions of the brain as well as near the cribriform plate. While all three regions are able to uptake CSF macromolecules, it is unknown how cells and fluid from the CSF-filled subarachnoid space gain access through the blood-CSF arachnoid barrier and into dural lymphatics. In this study, we expand on our previous findings demonstrating the capability of neuroinflammation-induced cribriform plate lymphangiogenic vessels in draining CSF and leukocytes. These lymphatics reside in an optimal location for CSF drainage due to gaps in the arachnoid epithelial layer separating the dura from the subarachnoid space and correlate with increased CSF accumulation near the cribriform plate during neuroinflammation. This is in contrast to other lymphatics residing in the dural layer dorsal and basal to the brain, which are separated from CSF by a complete and uninterrupted arachnoid layer. Additionally, we show lymphangiogenic cribriform plate lymphatic vessels dynamically up-regulate proteins to increase dendritic cell binding and T-cell tolerance during autoimmunity. These data identify cribriform plate lymphatic vessels as dynamic structures that are able to undergo lymphangiogenesis to facilitate fluid drainage and regulate adaptive immunity during neuroinflammation.

  PublisherDOI

• Cytokines and Chemokines in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

  The Journal of Immunology · 2020 · 46 citations

  1st authorCorresponding
  • Immunology
  • Biology

  T cells, neutrophils, B cells, monocytes, macrophages, and dendritic cells. The mechanism of immune-mediated inflammation in experimental autoimmune encephalomyelitis has been extensively studied in an effort to develop therapeutic modalities for multiple sclerosis and, indeed, has provided insight in modern drug discovery. The present Brief Review highlights critical pathogenic aspects of cytokines and chemokines involved in generation of effector T cell responses and migration of inflammatory cells to the CNS. Select cytokines and chemokines are certainly important in the regulatory response, which involves T regulatory, B regulatory, and myeloid-derived suppressor cells. However, that discussion is beyond the scope of this brief review.

  PublisherDOI

• Neuroinflammation functionally regulates CNS lymphatic vasculature and drainage

  The Journal of Immunology · 2019-05-01

  article

  Abstract There are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinflammation is not well understood. We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC – VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma. Lymphangiogenesis also contributes to the drainage of CNS derived antigens that leads to antigen specific T cell proliferation in the draining lymph nodes during EAE. In contrast, meningeal lymphatics do not undergo lymphangiogenesis during EAE, suggesting heterogeneity in CNS lymphatics. We conclude that increased lymphangiogenesis near the cribriform plate can contribute to the management of neuroinflammation-induced fluid accumulation and immune surveillance.

  PublisherDOI

• Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells

  Nature Communications · 2019-01-10 · 202 citations

  articleOpen access

  There are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinflammation is not well understood. We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC - VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma. Lymphangiogenesis also contributes to the drainage of CNS derived antigens that leads to antigen specific T cell proliferation in the draining lymph nodes during EAE. In contrast, meningeal lymphatics do not undergo lymphangiogenesis during EAE, suggesting heterogeneity in CNS lymphatics. We conclude that increased lymphangiogenesis near the cribriform plate can contribute to the management of neuroinflammation-induced fluid accumulation and immune surveillance.

  PublisherOA PDFDOI

• Delta-Like Ligand 4 (DLL4)/Notch axis regulates EAE development by modulating T cell trafficking across the blood brain barrier

  The Journal of Immunology · 2018-05-01 · 1 citations

  articleSenior author

  Abstract The Notch receptor system has been suggested to play a critical role in the regulation of chemokine receptor expression on encephalitogenic T cells and subsequent T cell trafficking to the central nervous system (CNS). Here we tested whether Delta-Like Ligand (DLL) 4 (DLL4)/Notch axis regulates EAE development by modulating T effector cell trafficking mechanisms across the blood-brain barrier (BBB). Primary cultures of brain microvessel endothelial cells were established and migration of splenocytes was tested in the presence of DLL4 blocking antibody. Our data show that anti DLL4 blocks transendothelial migration of non-activated T cells, but does not influence the migration of anti CD28 and CD3-activated splenocytes. Additionally, activation of brain microvessel endothelial cells with TNFα abrogated the blocking effect of anti DLL4 in transendothelial migration of T cells. We also demonstrate that blockade of DLL4 function inhibits the development of a progressive model of clinical experimental autoimmune encephalomyelitis (EAE), in C57Bl6 mice. Based on these results, we propose that endothelial DLL4 engagement with Notch expressing T cells is critical in strengthening the neuroinflammation and blockage of DLL4 could provide novel therapies in early phases of CNS neuroinflammatory diseases.

  PublisherDOI

• Issue Information – Editorial board & Publication schedule

  Cytometry Part A · 2018-07-01

  paratextOpen access

  Canada and Mexico); 2499 (Europe), 1978 (UK); $3869 (Rest of world). Online only: US $2645 (US, Canada, Mexico and Rest of world); 1708 (Europe), 1353 (UK). Prices are exclusive of tax. Asia-Pacific GST, Canadian GST

  PublisherOA PDFDOI

• Issue Information – Editorial board & PubSchedule

  Cytometry Part A · 2017-12-01

  paratextOpen access
  PublisherOA PDFDOI

• Issue Information – Editorial board & PubSchedule

  Cytometry Part A · 2017-10-01

  paratextOpen access
  PublisherOA PDFDOI

• Issue Information – Editorial board & PubSchedule

  Cytometry Part A · 2017-11-01

  paratextOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS034510

  NIH · $3.4M · 2011

• DLL4 Regulation of T Cell Migration in EAE

  NIH · $1.7M · 2013–2018

• NIH Grant P01NS023349

  NIH · $25.5M · 2008

• NIH Grant R01AI035934

  NIH · $2.2M · 2004

Frequent coauthors

• Stephen D. Miller

  Northwestern University

  27 shared

• Kevin J. Kennedy

  19 shared

• Nicholas W. Lukacs

  University of Michigan–Ann Arbor

  16 shared

• Brian T. Fife

  University of Minnesota

  14 shared

• Adam Elhofy

  14 shared

• Steven L. Kunkel

  University of Michigan–Ann Arbor

  10 shared

• Richard M. Ransohoff

  Third Dimension Technologies (United States)

  10 shared

• Mauro C. Dal Canto

  Northwestern University

  8 shared

Education

• Ph.D., Immunology-Microbiology

  Wayne State University

  1991

• BS, Biological Sciences

  Michigan Technological University

  1984