In a groundbreaking study published in the journal Cell on April 7, 2025, a research team from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, led by the esteemed Prof. Li Hanjie, has unveiled a remarkable and unexpected finding: the presence of microglia in the peripheral nervous system (PNS). This discovery is monumental as it challenges decades of established scientific understanding that has categorized microglia solely as components of the central nervous system (CNS).
Microglia are specialized immune cells known primarily for their roles in maintaining brain health, responding to injury, and participating in various neurological functions. Historically, these cells were presumed absent from the PNS, a belief rooted in extensive research primarily conducted with rodent models. However, the recent findings from Prof. Li’s team indicate that these immune cells play a crucial regulatory role even in peripheral neuronal structures, emphasizing the need to reassess long-held scientific tenets about microglial distribution and function across different nervous system compartments.
The journey toward this revolutionary discovery began with a 2023 study by the same research team, which successfully identified microglia in unusual locations such as human fetal skin, testicular tissues, and heart tissues. This initial inquiry raised pressing questions regarding the existence of microglia in the PNS and their specific roles therein. With growing evidence hinting at microglial involvement beyond the CNS, Prof. Li’s team embarked on a comprehensive investigation to determine if and how these vital immune cells are integrated into the PNS.
Employing a suite of advanced methodologies, including single-cell transcriptome sequencing, bioinformatics analyses, immunofluorescence staining, and functional assays, the researchers meticulously analyzed both human clinical samples and various animal models, including those derived from monkeys and pigs. Their multifaceted approach allowed them to gain profound insights into the molecular and structural attributes of PNS microglia, providing a sharper lens through which to view their evolutionary significance.
One of the pivotal outcomes of this study is the confirmation that PNS microglia exhibit a molecular signature, distinct protein markers, epigenetic profiles, and ontogenetic pathways that are strikingly similar to those present in their CNS counterparts. Prof. Li elaborated on this notable finding, emphasizing that such similarities contradict the long-held notion that microglia are exclusive to the CNS. Instead, the research illuminates the evolutionary continuity of microglial function and presence throughout vertebrates, shifting the paradigm of how scientists understand the role of immune cells in the nervous system.
In addition to elucidating the molecular identities of PNS microglia, the study also introduced a novel model conceptualizing the interaction among neuronal somas, PNS microglia, and satellite glial cells. The proposed triad mechanism replaces the traditional neuron-satellite glial cell duo model that has long been accepted in PNS research. This innovative framework reveals that PNS microglia actively enwrap neuronal somas in peripheral ganglia, thereby suggesting their integral role in both physiological and pathological contexts, including their rapid responses to fluctuations in neuronal activity.
Furthermore, the research unveiled an intriguing correlation regarding the evolutionary origins of PNS microglia. The abundance of these immune cells was found to be positively correlated with both the size of primary sensory neuron somas and the overall body size of the species being studied. Larger-bodied species tend to harbor a higher density of microglia surrounding their sensory neurons, while smaller animals exhibit a significantly reduced presence or complete absence of these important immune cells.
The study posits that this correlation could denote a strong selective pressure at play during vertebrate evolution. Species with larger peripheral neuronal somas rely on microglia for essential processes, including soma enlargement during neuronal maturation, which may, in turn, affect their ability to adapt to environmental changes. These findings suggest that as body and neuronal sizes increased through evolutionary processes, the need for PNS microglia to support and regulate these changes became paramount.
Dr. Wu Zhisheng, the principal author of the study, highlighted the considerable implications of their findings for future research and understanding of neuroimmune interactions. Their research not only uncovers the ontogeny and evolutionary aspects of PNS microglia but also broadens the horizons for investigations into their regulatory roles regarding neuron size and function. This newfound understanding opens up exciting avenues for future therapies targeted at neurodegenerative diseases, injuries, and other pathological conditions affecting the nervous system.
The research conducted by Prof. Li and his team thus serves as a comprehensive call to reevaluate existing neurobiological paradigms and encourages a more integrative approach to studying microglia throughout both central and peripheral neural systems. As scientists continue to glean insights from these remarkable findings, the implications may extend far beyond understanding basic neurobiology, potentially transforming therapeutic strategies for a range of neurological disorders while reshaping the framework for studying the immune composition of the nervous system.
This landmark study not only enriches our understanding of microglial biology but also emphasizes the importance of interdisciplinary approaches in uncovering the complexities of the nervous system. As the scientific community digests this revolutionary work, we may witness an era of accelerated research focusing on the dual roles of immune cells in both central and peripheral contexts—a shift that could redefine many aspects of neuroscience in the years to come.
The study sheds light on the intricate interplay between evolutionary biology and neuroimmunology, further illustrating how adaptations have shaped the functional repertoire of microglia across different tissues. As research advances, it is anticipated that the revelation of PNS microglia will catalyze renewed interest in exploring the mechanisms by which these cells communicate within the nerve microenvironment, ultimately fostering a deeper understanding of their relevance in health and disease.
Through these findings, the dynamic and multifaceted landscape of the nervous system becomes increasingly apparent—one where immune cells no longer remain merely as passive observers but rather emerge as vital actors influencing neuronal development and activity. The implications of this study extend beyond a novel finding; it represents a paradigm shift that could redefine our understanding of neuroimmunology at large.
As we await further advancements in this burgeoning field, the future promises expanding horizons for exploring the roles of immune cells within all facets of neural architecture, ultimately paving the way for innovative therapeutic interventions designed to enhance neuronal function and resilience.
Subject of Research: Microglia in the Peripheral Nervous System
Article Title: Discovery of Microglia in the Peripheral Nervous System by Prof. Li Hanjie’s Team
News Publication Date: April 7, 2025
Web References: Cell Journal
References: Cell Journal
Image Credits: Not available
Keywords
Microglia, Peripheral Nervous System, Evolutionary Biology, Neuroimmunology, Neuronal Development, Immune Cells.
