The relationship between the immune system and nervous system, also known as the neuroimmune axis, has long been recognized as critical in understanding the complex mechanisms behind skin sensations, inflammation, and immune responses. Despite its establishment, researchers continue to unravel the intricacies of this relationship, shedding light on how it could provide new avenues for treating a variety of sensory, inflammatory, and infectious diseases. Here, we present an in-depth discussion based on interdisciplinary studies, including insights from a 2019 article published in the Journal of Immunology by Trier Anna M. and colleagues, associated with the Center for the Study of Itch at Washington University School of Medicine. The article, with a DOI of 10.4049/jimmunol.1801473, emphasizes the importance of neuroimmune interactions and how they underpin the diverse pathologies of itch and pain sensations, providing transformative understanding of the immune and nervous systems’ collaborative roles.
Keywords
1. Neuroimmune axis
2. Skin inflammation
3. Itch biology
4. Immune cytokines
5. Sensory neurons
The Neuroimmune Axis in Skin Sensation, Inflammation, and Immunity
The relationship between our nervous system, the intricate network carrying messages to and from the brain to every part of our body, and our immune system, our body’s defense against infections and diseases, is referred to as the neuroimmune axis. This axis plays a crucial role in maintaining homeostasis and responding to external stimuli. Recent interdisciplinary studies have shed new light on how this relationship plays a specific role in skin sensation, inflammation, and immunity, which could eventually lead to innovative treatments for various conditions.
Anna M. Trier, Madison R. Mack, and Brian S. Kim of the Center for the Study of Itch and the Division of Dermatology at Washington University School of Medicine’s immersive research published in 2019 [DOI: 10.4049/jimmunol.1801473], funded by the National Institutes of Health [K08 AR065577, R01 AR070116, T32 AI007163], uncovers crucial aspects of the bidirectional communication between the immune and nervous systems, particularly in relation to itch and pain biology.
Sensory Neurons and Inflammation: A Two-Way Street
The sensation of pain or itch is not just a message sent from the skin to the brain; it is a complex dialogue involving immune cells and sensory neurons. According to Pinho-Ribeiro, Verri, and Chiu (2017), nociceptor sensory neurons engage in cross-talk with immune cells, influencing pain and inflammation [PMC5205568]. These interactions are pivotal in shaping the perception and response to painful stimuli. Similarly, Cook et al. (2018) suggest that immune cytokines and their receptors play a significant role in the modulation of inflammatory pain [DOI: 10.1016/j.it.2018.02.007].
The research by Trier and colleagues extends these findings by detailing the mechanisms through which inflammatory cytokines such as interleukins, tumor necrosis factor-alpha (TNF-α), and other inflammatory mediators influence sensory neurons to evoke itch and pain. The study also posits that sensory neurons reciprocally regulate the function of immune cells, illustrating the complexity of this neuroimmune communication.
From Itch to Immune Response: The Interplay of Cells and Signals
Itch, medically known as pruritus, provides a model to understand these interactions. Azimi, Xia, and Lerner (2016) elucidate peripheral itch mechanisms, identifying various molecules and pathways involved in the sensation [PMC5540324]. Moreover, the neurobiology of itch, as explained by Ikoma et al. (2006), involves an assortment of receptors and channels on sensory neurons, responding to environmental and physiological changes, resulting in the itching sensation [DOI: 10.1038/nrn1950].
Furthermore, Meng and Steinhoff (2016) discuss the molecular mechanisms of pruritus, providing insight into how immune-related changes can lead to chronic itching and related skin conditions [DOI: 10.1016/j.retram.2016.09.002]. This relationship is also influenced by various types of receptors and channels, such as transient receptor potential (TRP) channels, which have been implicated in sensing itch and pain signals (Sun and Dong, 2016) [PMC4798920].
The Impact of Itch Biology on Disease Understanding
Scratching the surface of itch biology not only improves our basic understanding of this common sensation but also has implications for disease understanding. Chronic itch can be a debilitating symptom of many inflammatory and infectious diseases, and by elucidating the underlying causes, treatments can be better targeted. For instance, emerging therapies that modulate immune cytokines or directly target sensory neurons offer potential for relief from chronic itch and related disorders. Trier and colleagues highlight this connection, exploring how understanding itch can inform broader treatment strategies across various sensory, inflammatory, and infectious diseases.
Future Implications and Clinical Applications
The collaboration of the immune and nervous systems in the context of skin sensation and disease is an area ripe for clinical innovation. With a better understanding of the neuroimmune axis, researchers are developing new treatment modalities aimed at managing conditions such as atopic dermatitis, psoriasis, and other diseases that have both an immune and sensory component.
Potential pathways for future research include the drugs targeting interleukin receptors and JAK/STAT pathways which are already showing promise in treating inflammatory diseases with a sensory component [DOI: 10.1016/j.jaci.2016.12.981]. The 2019 study by Trier et al. signals the rise of interdisciplinary approaches rooted in neuroimmunology, setting a new frontier for treating difficult-to-manage conditions.
Conclusion
The work of Trier and her team opens new doorways into our understanding of the neuroimmune axis and its implications for inflammatory, infectious, and sensory diseases. Recent research has provided a more intimate look at how our defense mechanisms and sensory signals interlace, ushering a new age of targeted therapies and improved quality of life for patients with related conditions.
As research unfolds, we continue to understand how these systems communicate and the potential to modulate this communication to our advantage—a reminder of the body’s remarkable complexity and the endless possibilities for scientific discovery.
References
1. Trier, A. M., Mack, M. R., Kim, B. S. (2019). The Neuroimmune Axis in Skin Sensation, Inflammation, and Immunity. J Immunol, 202(10), 2829–2835. https://doi.org/10.4049/jimmunol.1801473
2. Pinho-Ribeiro, F. A., Verri, W. A. Jr., Chiu, I. M. (2017). Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation. Trends Immunol, 38(1), 5-19. https://doi.org/10.1016/j.it.2016.10.001
3. Cook, A. D., Christensen, A. D., Tewari, D., McMahon, S. B., Hamilton, J. A. (2018). Immune Cytokines and Their Receptors in Inflammatory Pain. Trends Immunol, 39(3), 240-255. https://doi.org/10.1016/j.it.2018.02.007
4. Azimi, E., Xia, J., Lerner, E. A. (2016). Peripheral Mechanisms of Itch. Curr. Probl. Dermatol, 50, 18-23. https://doi.org/10.1159/000446056
5. Ikoma, A., Steinhoff, M., Ständer, S., Yosipovitch, G., Schmelz, M. (2006). The neurobiology of itch. Nat. Rev. Neurosci, 7(7), 535-547. https://doi.org/10.1038/nrn1950