Versiti - Bonnie N. Dittel, PhD | Versiti Blood Research Institute

Bonnie N. Dittel, PhD

Bonnie N. Bonnie N. profile

Bonnie N. Dittel, PhD

Senior Investigator

Immunobiology

Dr. Gilbert C. White II Endowed Faculty Chair

Professor
Department of Microbiology & Immunology
Medical College of Wisconsin

Education and Training

Postdoctoral Training
Yale University

Doctoral Training
University of Minnesota, Ph.D., 1994

Immunobiology

The focus of our research program is to investigate cellular and molecular mechanisms involved in the regulation of inflammation. Inflammation is a component of virtually every disease and if not controlled can lead to severe tissue damage. The primary disease model utilized in the laboratory is the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). MS is an autoimmune disorder of the central nervous system (CNS) and is characterized by focal areas of inflammation. In past studies, we have extensively utilized EAE to study negative immune regulatory mechanisms that keep inflammation in check within the CNS. Our current studies have expanded to mouse models of contact dermatitis (contact hypersensitivity) and inflammatory bowel disease (DSS-colitis). 

Current Research Interests

Regulatory B cells (Breg)

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. In our studies, we have found that B cells regulate the severity of EAE by interactions with Foxp3+ T regulatory cells (Treg) in a GITRL-dependent manner. Specifically, we found that B cells play an essential role in Treg homeostasis whereby they maintain Treg numbers at a sufficient level to dampen inflammation. Current studies are investigating the development, phenotype and localization of this novel subset of regulatory B cells. These studies utilize the EAE and contact hypersensitivity models. The goal of this research is to undercover a novel Breg subset that can be exploited for cell-based therapies for the treatment of inflammatory disorders.

Myeloperoxidase (MPO)

MPO is a myeloid-lineage restricted enzyme that utilizes H2O2 to generate hypochlorous acid that has strong antibacterial properties. In sterile inflammation, such as MS, MPO and MPO-derived oxidants are thought to be pathogenic promoting inflammation and causing tissue damage. In particular, MPO has been implicated in vascular permeability. In MS, the opening of the blood-brain barrier (BBB) is considered detrimental. The presence of MPO within inflammatory lesions in MS patients along with our studies in the EAE model, suggests that it plays a pathogenic role in MS. Using a novel inhibitor of MPO, we have found that its inhibition during EAE rapidly attenuates disease severity that is associated with sealing of the BBB. Current studies in the lab are focused on the pathogenic role of MPO in inflammation with an emphasis on vascular permeability. In addition to EAE, these studies also utilize the contact hypersensitivity and DSS-colitis models in which permeability is also considered pathogenic. The goal of this research is to undercover the mechanism whereby MPO induces vascular and epithelial permeability and to determine whether MPO is a viable therapeutic target for the treatment of inflammatory diseases.

Microbiome

It is now clear that interactions between the immune system and microbiome have consequences for human health. In past studies, we utilized microbiome analysis to study microbial dysbiosis in the gut in IL-10-deficient mice. In current studies, we are utilizing this knowledge and expertise to determine how

  • 1R56AI122655 - 01A1, NIAID, Mechanisms of a novel regulatory B cell subset  
  • 1R56AI129348-01A1, NIAID, B cell-mediated immune regulation
  • Teva Investigator Sponsored Studies, Teva Pharmaceuticals, Access the ability of Copaxone to enhance the regulatory activity of a novel B cell subset
  • RG 1501-03034, National Multiple Sclerosis Society, Characterization of a Novel Regulatory B Cell Subset that Attenuates EAE
  • Medical College of Wisconsin, Cancer Center pilot grant, Can chronic lymphocytic leukemia (CLL) exhibit regulatory B cell function?

Cody Gurski
Research Technologist

Nathan Meinardt  
Postdoc

Angela Beltrame
Graduate Student 

Kelli Cole
Graduate Student 

Regulatory B cells

Myeloperoxidase

Microbiome

 
Immunobiology
We study the development and function of the immune system and design immunomodulating therapies for infection, autoimmune disease, and cancer.
 
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