Unlocking the Secrets of Neuroimmunology: Connecting What Belongs Together

2022 Bio-Rad Science Writing Competition Joint 2nd Place

Patrick’s passion for understanding the intertwining topics of neurology and immunology is evident in his neuroimmunology article. The judges were impressed with his honest descriptions of the joys and drawbacks of being part of interdisciplinary research.

Patrick is a PhD student in the program of the International Max Planck Research School for Immunobiology, Epigenetics and Metabolism (IMPRS-IEM). He is a researcher in the field of neuroimmunology, investigating the relationship and cross-regulation of the immune system and nervous system. At the moment, he conducts his research in the Institute for Systems Immunology in Würzburg, Germany.

We are delighted to publish his entry below:

For a long time, immunology and neuroscience have been considered two separate fields of research, like a couple of strangers who just happened to meet on the same bus. Immunology focuses on the body's defense system, while neuroscience studies the nervous system, that is the entity that makes you feel, think and understand. But recently, something unexpected has happened  —  the two have started to talk during their ride  —  and that has formed something exciting! The field of research, neuroimmunology.

One of the key aspects of neuroimmunology is understanding how two parts become one system. For a long time, we have considered different research fields as distinct entities without seeing their connection. As shown in figure one, we can distinguish various anatomical and functional areas but actually they are closely linked. Indeed, research has shown that the nervous system can modulate the immune response while immune cells can make nerve cells more excitable (Marchand et al. 2005). Let’s dive a bit deeper:

Fig 1. One system made up of several parts. So far, science has often considered different “systems” within our body. However, those are closely linked and working together as one within each living being.

Lots of research has been focused on nerve activity and its effect on immune cells. Let’s use the skin as an example as it not only acts as a barrier against pathogens but also as a communication interface for our perception of the world (just think about touch, temperature, pain). The skin is innervated by a network of nerves that send signals to and from the brain. These signals can appear in the form of short amino acid chains called neuropeptides. Have you ever heard of CGRP? No, it’s not a new type of cheese! CGRP stands for “calcitonin gene-related peptide”  —  a small peptide that plays a key role in neuroimmunology in the skin. For example, the release of certain neuropeptides, such as CGRP, can regulate the production of cytokines (the communication molecules of the immune system) and thus, how infections are fought off (Blake et al. 2019, Cohen et al. 2019). Neuropeptides in the skin also play essential roles in the repair of tissue damage. For example, Gouilly et al. have shown that another neuropeptide, TAFA4, can promote the help of macrophages in healing sunburn damaged skin (Hoeffel et al. 2021). However, it should be noted that different types of damage might need different kinds of responses for optimal healing. However, figure 2 presents a scheme visualizing that various functions originally associated with a distinct “system” are actually a process depending on tight cross-regulation.

Fig 2. Physiological processes are an amalgam of nervous and immune system function. Indeed, even feelings like fear can be driven by immunological triggers (Rossi et al. 2012, Michopoulos et al. 2017). This shows that processes such as immunity are not just dependent on our immune system but also need regulation by the nervous system.

I am very happy to be allowed to witness the growing importance of interdisciplinary research, especially in neuroimmunology. The study of interactions between the nervous system and the immune system is complex and requires a deep understanding of methods from two different fields. Also, communicating effectively in this context can be challenging because each scientist may have a deep understanding of the topic they specialize in, but may not be as familiar with the other areas being studied. This can lead to difficulties in understanding each other's perspectives and methods, making it harder to collaborate and share information. However, after many years of volunteering in scientific initiatives, I found that by approaching the conversation with a positive attitude, you can help to build rapport and create a more relaxed and open atmosphere. By the same token as:

“Why did the physicist cross the road? — To get to the other side of the equation!” It is often useful to assume the perspective of your counterpart and use analogies or simple examples to explain complex concepts and be willing to ask questions that might help them to follow.

However, I have come to realize that this challenge is part of what makes this field so rewarding. It is only through mastering the complexities of both neuroscience and immunology that we can truly understand how our body works. This has made me even more passionate about my research, as I strive to better understand how these two fields are intertwined. 

After having mastered the “soft problems” with soft skills, let’s get to the hard problems of what questions remain to be answered (hopefully with my contribution). You know that feeling of a light touch on your skin? Or when something itches? That’s your sensory nerve terminals at work!

Sensory nerve terminals are the little nerve endings that detect sensations on our skin. They’re like tiny sensors that pick up on things such as heat, cold, and pressure. They send signals to the brain telling it what’s happening, so that you can react appropriately. But here’s the thing: I’m researching whether immune cells can activate these sensory nerve terminals! Can you imagine that your immune cells are in charge of your sense of touch? Indeed, it was shown that overall inflammation can change their tendency to be activated by known stimuli (Watkins et al. 2008, Duzhyy et al. 2021). My research is focused on how immune cells interact with the nerve cells in the skin to activate them when only immune triggering substances are present, using mice as a means to activate immune cells and see if neurons upregulate a certain set of transcripts and proteins. For everyone who might be lost, the experimental design looks something like:

Trigger for the immune system — immune cell — mediator — receptor on neuron—neuronal response.

In conclusion, this blog should be a reminder to consider our physiology as a united system! Interestingly, even skin cells (not neurons!) contribute to feel temperature (Sadler et al. 2020). By the same token, we will learn much more about how our body actually functions when blending the “boarders” of various research areas together.