Team Sulzer

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Neuro-immune Interactions | 2020

Adaptive Immunity in the Etiology and Progression of Parkinson’s Disease

Study Rationale: Research from Team Sulzer indicates that immune cells may play central roles in the development of Parkinson’s disease (PD). In PD, certain types of nerve cells can activate specific types of immune cells (known as T cells, which are found in the blood and lymph nodes). These T cells may kill nerve cells in PD patients’ gastrointestinal tract and brain, and the loss of nerve cells contributes to the symptoms of PD. These immunological responses will be studied in animal models and human tissue including the brains of PD patients.

Hypothesis: Team Sulzer proposes that, in PD, these activated T cells mistake the body’s normal nerve cells as foreign invaders (autoimmunity) and this error is critical in the initiation of PD. The interactions of T cells with nerve cells underlies the loss of specific neurons in PD, including substantia nigra dopamine neurons.

Study Design: Team Sulzer will determine the steps that occur in T cell activation in PD by examining T cells in blood from PD patients and healthy controls, and in the gut and brain of new mouse models of PD. To examine if these cell types are in human brain, Team Sulzer has developed new methods to detect signals in specific cells in autopsies of PD patients.

Impact on Diagnosis/Treatment of Parkinson’s Disease: The T cells and the molecules they use to interact with nerve cells can be used to identify people with PD before they develop symptoms, to identify ways to predict the progression of PD, treatments optimal for specific patients, and to provide new therapies by blocking steps in immune responses.

Leadership
David Sulzer, PhD
COORDINATING LEAD PI

David Sulzer, PhD

Columbia University
Ashley Harms, PhD
CO-INVESTIGATOR

Ashley Harms, PhD

University of Alabama at Birmingham
Cecilia Arlehamn, PhD
CO-INVESTIGATOR

Cecilia Arlehamn, PhD

La Jolla Institute for Immunology
Sarkis Mazmanian, PhD
Co-Investigator

Sarkis Mazmanian, PhD

California Institute of Technology
Kim (Ngan) Tran, BA
Project Manager

Kim (Ngan) Tran, BA

Columbia University Medical Center

Project Outcomes

Team Sulzer expects this unique nexus of microbiology, immunology, and neuroscience to make critical contributions to unraveling PD pathogenesis by defining the role of the adaptive immune system, potentially informing the development of novel therapeutic approaches. View Team Outcomes.

Team Outputs

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Overall Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of November 2023. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific theme.

Impact

Theme

Featured Output

Below is an example of a research output from the team that contributes to the ASAP mission of accelerating discoveries for PD.

Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease

Team Sulzer has worked to uncover the role of border-associated macrophages (BAMs) in Parkinson’s disease. These immune cells, which earned their name by residing at the border of the brain and periphery, mediate antigen presentation and immune infiltration to the brain. In Parkinson’s disease, it was found that there is an increased interaction between BAMs and the immune cells that infiltrate the brain. The results from this study identify a critical cell type that mediates the process of peripheral immune infiltration to the brain and antigen presentation to CD4+ T cells, which is known to contribute to synuclein-mediated neurodegeneration.

Team Accolades

Members of the team have been recognized for their contributions.

Other Team Activities

  • Working Groups: Microbiome – Sarkis Mazmanian (Co-Chair), Osama Al Dalahmah (Subgroup Lead)
  • Interest Groups: PD Modeling – Rodent & Fly Models – Ashley Harms (Co-Chair)

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