Dr. Pierre Cunin – Neutrophils: Quick Change Artists

Dr. Pierre Cunin – Neutrophils: Quick Change Artists

Although much has been done to improve our understanding of autoimmune conditions, large knowledge gaps still exist, meaning that some conditions are still poorly understood. The  pathophysiology (altered physiological processes associated with disease or injury), in particular, requires a great deal more scrutiny to garner an improved understanding of how it contributes to disease and disease symptoms. Part of the reason why autoimmune/inflammatory research is a complex field is the variety of cell lineages involved in the development of such conditions. Macrophages, B and T lymphocytes, mast cells, neutrophils, and most recently platelets and megakaryocytes have all been found to be contributors to the development and progression of these  conditions. Understanding the role of these cell types in joint injury and how the immune cells interact and communicate, aggravating inflammatory conditions such as arthritis, will undoubtedly offer opportunities to discover novel drug targets and improve patient outcomes.

Bridging the Gap

Dr Cunin is an instructor in medicine at Harvard Medical School and has undertaken several training posts in research laboratories, including the Curie Institute and the University of Bath. Based on a great need to fill in these knowledge gaps, Dr Cunin has focused his research on understanding the fundamental mechanisms of immune cells in inflammatory diseases. By unravelling the role some of the above-mentioned cell types have in the development and progression of inflammatory conditions Dr Cunin hopes to identify new therapeutic targets.

The Ins and Outs of Emperipolesis

As an ANRF scholar he has concentrated on an intriguing biological phenomenon, termed emperipolesis.  Megakaryocytes are large bone marrow cells that produce and release platelets into circulation. Emperipolesis occurs when these megakaryocytes directly interact with immune cells in the bone marrow. Neutrophils, the foot soldiers of immunity, are taken up by the megakaryocytes, move through the cytoplasm of these cells and ultimately are released back into their environment, without any harm to either cells. Observed for the first time 50 years ago, this cell-in-cell interaction is still poorly-characterized, and its physiological significance remains to be found.

Inflammation on the Rise

Research by the laboratory showed that emperipolesis significantly increases in several inflammatory mouse models, including during inflammatory arthritis. Interestingly, the phenotype of neutrophils is strongly modified after their passage into megakaryocytes. Megakaryocytes can transfer biological material into the neutrophils as they migrate through their cytoplasm, likely in order to prepare neutrophils to promote inflammation. Interestingly, he found that emperipolesis is increased in patients with arthritis. Therefore, pharmacological manipulation of emperipolesis may have significant implications for arthritis and other neutrophil-driven inflammatory disorder treatment strategies. This research has also been elemental in defining a new role for megakaryocytes as immune cells in their own right as well providing insights into the overlap of haematology and immunology, both areas of research critical to the study of arthritis.

A Smoking Gun

Based on this data and the team’s observations, they are now interested in better defining the molecular mechanism occurring during this interaction. In particular, they hope to characterize the immune arsenal transferred by the megakaryocyte into neutrophils. More importantly, they will be trying to identify inflammatory triggers responsible for the increased emperipolesis during inflammatory conditions, as well as specific inhibitors or activators for emperipolesis. The ultimate goal would be to therapeutically manipulate the process in inflammatory and autoimmune diseases, and potentially in other diseases states in which emperipolesis is increased to create improved treatment outcomes.

“For a long time, emperipolesis was considered as a histological curiosity in the bone marrow. However, our work established a very important and unprecedented process in which the inflammatory capacities of neutrophils are modified. These findings will contribute to a fundamental change in our understanding of megakaryocytes as participants in immunity. More importantly, the observation that emperipolesis increases in systemic inflammation potentially opens new avenues for intervention in inflammatory arthritis.” – Dr Pierre Cunin

Better Together

A number of peer reviewed articles based on these findings were accepted and published in prestigious journals. The grant received by the ANRF was also instrumental in allowing Dr Cunin to hire a technical research assistant, dedicated to the support of this project. This demonstrates the way in which these grants create a community of researchers striving towards the same goal. There are not many silver linings in 2020 but one of the few is that the combined efforts of the scientific communities have shown just how much can be achieved through collaborative efforts. Working towards a common goal as a community has always been a cornerstone of the ANRF’s ethos and as we move forward, we know a great deal can be achieved if we continue to approach research in this manner. Together we can find a cure!

If you missed our November edition head over to https://curearthritis.org/arthritis-research-scientists-2020-2021 to find out which scientists we will be collaborating with and how they plan to positively improve the autoimmune research landscape!

Article Author
Arthritis National Research Foundation

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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