Bonnie N. Dittel, PhD

Senior Investigator
Blood Research Institute
BloodCenter of Wisconsin
Adjunct Faculty
Department of Microbiology and Molecular Genetics
Medical College of Wisconsin
Education and Training
Postdoctoral Training
Yale University
Doctoral Training
University of Minnesota, Ph.D., 1994
Contact Information
Phone: (414) 937-3865
Fax: (414) 937-6284

The goal of my research program is to investigate the cellular and molecular mechanisms involved in the regulation of the autoimmune immune response. Broadly, we are studying how the immune system regulates inflammation associated with autoimmunity in the central nervous system (CNS) (brain and spinal cord). To study the regulation of inflammation associated with an autoimmune attack in the CNS, we are using the rodent model of the human autoimmune disease multiple sclerosis (MS), termed experimental autoimmune encephalomyelitis (EAE). Autoimmunity is a serious immunological disorder with devastating clinical consequences and occurs when a person’s own immune system inappropriately reacts against their own tissues. In the case of MS, which is thought to be an autoimmune disease of the CNS, patients mount a T cell response against protein found in the myelin sheath covering nerve axons. MS patients exhibit a wide variety of neurological symptoms, including muscle weakness and changes in vision and memory. In the study of MS, advances in understanding the disease process have been facilitated using the EAE model. EAE is a CD4 T cell-mediated autoimmune disease and like MS is characterized by the accumulation of immune cells in the CNS.
Regulatory B cells
B cell regulation of autoimmunity was first demonstrated in the EAE model, whereby mice deficient in B cells were unable to recover from the clinical signs of EAE. We are studying the mechanism of this B cell regulation with an emphasis on interactions between B cells and Foxp3+ T regulatory cells.
Microglial Cell Regulation of Autoimmunity
In our studies examining initiation of EAE disease, we have extensively studied the role of microglial cells and how they become activated by self-reactive T cells. Microglial cells are from the myeloid lineage and are resident to the CNS existing in a resting state characterized by a ramified morphology. However, upon activation, microglial cells alter both their morphology and phenotype. Currently, we are studying the role of B7 on microglial cells in controlling the extent of inflammation in the CNS.
T Cell-Neuronal Interactions
Although both EAE and MS are considered to be demyelinating diseases, not all of the clinical symptoms can be explained by just the loss of the myelin sheath in localized lesions. Indeed, it is known that damage to the nerves themselves can be observed in both MS and EAE. Thus we are studying whether the encephalitogenic T cells may directly interact with neurons. Our preliminary studies show that they do, resulting in neuronal dysfunction. We are currently investigating the mechanism of immune-mediated neuronal dysfunction.
Cannabinoid System

We are also examining the role of the endogenous cannabinoid system in the CNS during EAE. The cannabinoid system was first discovered because the active ingredient in marijuana, THC, binds to receptors in the brain. Now it is known that the endocannabinoid system can both positively and negatively regulate immune cell functions. We are studying how the endocannabinoid system regulates T cell-mediated inflammation in the CNS and its impact on peripheral B cell responses.

  • NIAID R01AI69358, "The Role of B Cells in Regulating Autoimmunity"
  • National Multiple Sclerosis Society, RG 4432-A-5, “Elucidating the role of cannabinoid receptor 2 in immune regulation during EAE”
  • National Multiple Sclerosis Society, RG 4629-A-6, "Regulation of EAE by CD86 expressed within the CNS"
  • Department of Veteran Affairs, “Freeze-Dried Blueberries: Prevention and Rehabilitation Strategies in MS”

Avijit Ray, PhD

Reserach Scientist I
Nichole Miller
Research Technologist
Shelley Morris-Islo

Laboratory Technician

Selected Publications
  • Ponomarev, E.D., L.P. Shriver, K. Maresz, and B.N. Dittel. 2005. Microglial cell activation and proliferation precedes the onset of CNS Autoimmunity. J. Neurosci Res. 81:374-389.
  • Maresz, K., E.J. Carrier, E.D. Ponomarev, C.J. Hillard, and B.N. Dittel. 2005. Modulation of the endocannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J. Neurochem. 95:437-445.
  • Shriver, L.P. and B.N. Dittel. 2006. T cell-mediated disruption of the neuronal microtubule network: Correlation with early reversible axonal dysfunction in acute experimental autoimmune encephalomyelitis. Amer. J. Path. 169:999-1011.
  • Mann, M.K., K. Maresz, L.P. Shriver, T. Tan, and B.N. Dittel. 2007. B cell regulation of CD4+CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J. Immunol. 178:3447-3456.
  • Maresz, K. G. Pryce, E.D. Ponomarev, G. Marsicano, J.L. Croxford, L.P. Shriver, C. Ledent, X. Cheng, E. Carrier, Mann, M.K., G. Giovannoni, R.G. Pertwee, T. Yamamura, N.E. Buckley, C.J. Hillard, B. Lutz, D. Baker and B.N. Dittel. 2007. Direct Suppression of CNS Autoimmune Inflammation Via the Cannabinoid Receptor CB1 on Neurons and CB2 on Autoreactive T Cells. Nat. Med. 13:492-497.
  • Ponomarev, E.D., K. Maresz, Y. Tan and B.N. Dittel. 2007. CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. J. Neurosci. 27:10714-10721.
  • Ray, A., M.K. Mann, S. Basu, and B.N. Dittel. 2011. A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J. Neuroimmunol. 230:1-9.
  • Basu, S., Ray, A, and B.N. Dittel. 2011. Cannabinoid receptor 2 (CB2) is critical for the homing and retention of marginal zone B lineage cells and for efficient T-independent immune responses. J. Immunol. 187:5720-5732.

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