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DAT and TH expressing myeloid-derived suppressor cells are increased in Parkinson's Disease

Basil Hashimi and Martin Badov

Authors:  Basil Hashimi, Adithya Gopinath, Martin Badov, Madison Francis, Michael Okun, Wolfgang J. Streit, Habibeh Khoshboeui

Faculty Mentor:  Habibeh Khoshboeui

College:  College of Medicine

Abstract

Parkinson’s disease (PD) is characterized by dopaminergic degeneration and is thought to start in the periphery. The nature of communication between the periphery and central nervous system (CNS) remains unclear. Peripheral immune cells express key dopaminergic proteins, including dopamine transporter (DAT) and tyrosine hydroxylase (TH), and may be regulated by CNS-produced dopamine. After establishing a novel flow cytometry protocol to detect DAT, TH, and CD14 expression in the monocytes of PD patients, we made the surprising discovery of increased DAT/TH+ and CD14+ monocytes in PD patients versus healthy controls. We next hypothesized that the CD14+ monocyte population in PD patients is composed of multiple subsets of monocytes, including myeloid-derived suppressor cells (MDSCs), capable of altering the immune landscape through infiltration. Extensive characterization of the altered monocyte population revealed that CD14+ HLA-DR(-) monocytes, defined as monocytic-MDSCs, are significantly elevated in PD patients. This population, capable of inhibiting immune function of other immune cells system wide, supports the interpretation that there are specific monocyte populations which could be involved in the mechanistic relationship between the peripheral immune system and changes in CNS dopamine in PD.

Poster Pitch

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Poster

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18 Responses
  1. Franz Nartatez

    Cool and really interesting research! The future looks bright with students like you doing this kind of research!

  3. Alexa M

    This is very profound!! I like it a lot.
    What exactly is meant by the statement that this monocytic population is involved in altering other immune responses throughout the system? Could a downregulation of these cells then cause a slow in the progression of the disease in the CNS? Or just in the periphery?

    Thanks!!

    1. Basil Hashimi

      Hey Alexa, Thank you for your question!

      What we mean when we say that “this monocytic population is involved in altering other immune responses throughout the system” is that the subset of CD14+ monocytes, which we identified as MDSCs (through flow cytometric analysis of biomarkers), have a regulatory role in the innate and adaptive immune systems, as referenced in the video. For example, MDSCs can emit certain cytokines which can induce naive T-cells into expressing a regulatory T cell phenotype, which is known to suppress activity of T helper cells. Our future studies are hoping to explore the exact role of MDSCs in immunosuppression and it is quite possible that a down-regulation of these cells can cause a slow progression of PD in the CNS and/or the periphery. By investigating the exact immunological effects and methods of MDSCs in immune suppression we are looking to establish therapeutic targets, whether it be the innate or adaptive immune system, in combating PD progression. In an ideal world, we hope to diagnose PD early through peripheral monocyte analysis and then target various monocytic cell types to prevent progression of PD. Our lab is excited to explore this pathology further!

      Thank you again for your question!

      1. Sarim Mobin

        This is a very interesting finding!!It gives us more insight to the physiological factors in Parkinson’s disease.

  5. Zeeshan Malik

    This is super interesting! This has great potential in forming an understanding of the link between the different systems in our body.

  6. Ahmed Jafri

    Really interesting research! This should help find new ways to treat Parkinson’s disease.

  8. Himani Gubbi

    Very interesting research and very well presented! Does the increase in MDSC population you found in PD patients manifest pathologically? How this globally altered immunological state impact the symptoms experienced by a PD patient? Thanks

    1. Basil Hashimi

      Thank you Himani!

      So as of right now we cannot make any specific conclusions regarding an elevation of MDSCs to pathological manifestations of PD. We have found that PD patients who exhibit typical motor symptoms do have elevated MDSCs compared to healthy controls, but we cannot be certain that the symptoms manifest solely due to the elevation of MDSCs. There seems to be a significant connection though. Overall, we hypothesize that the globally altered immunological state has an impact on PD patient symptoms as there is a correlation between immune dysregulation and PD pathology. Our current studies have not explored the extent of immune dysregulation to symptom severity, but this is a great question and may be a topic that our lab may look to explore in the future.

      1. Martin Badov

        Thank you again for the question! I would just like to add a small comment regarding the pathological implications of MDSCs in PD. While we don’t understand exactly how MDSCs influence PD pathology, it has been observed that MDSCs can suppress the immune system in other conditions such as cancer. MDSCs may play a role in the tumor’s ability to evade the immune surveillance. We hypothesize that MDSCs play some sort of immunosuppressive role in PD, which may possibly limit our body’s ability to effectively respond to immune dysregulation. This is part of the reason why we plan to examine regulatory T cells – which also play an immunosuppressive role – in future experiments!

  9. Abhaya Dilip

    Hi, Basil! This is incredible work. Prior to watching your presentation, I never thought to consider the immune system as having a role in the development of Parkinson’s Disease (PD). Do you think that immunosuppressants would be beneficial to administer prophylactically to patients at-risk of developing PD or for those who already have PD, to slow the progression of their disease?

    -Abhaya Dilip

    1. Martin Badov

      Excellent question! Unfortunately we don’t understand role of the immune system in PD well enough to make any concrete conclusions. Since PD is a neuroinflammatory disease, it is possible that these suppressive immune cells are elevated in an effort to restore homeostasis. However, it is also possible that MDSCs may actually be contributing to the progression of the disease. This is something we hope to answer in future experiments, where we will further explore changes in the immune system under disease conditions.