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Connections between the nervous and immune systems are increasingly recognized as central to brain-body physiology. In this Review, we examine how these systems collaborate to detect and respond to both internal and external stimuli - such as psychological stress, circadian cues, infection, and tissue injury. Rather than operating in isolation, the nervous and immune systems form an integrated network that is more than the sum of its parts. They share a common architecture and vocabulary, enabling bidirectional connection and communication that modulate immune cell characteristics throughout the body. We review immune-nervous interactions within two complementary frameworks: first, a spatial framework that distinguishes communication in the brain, communication within peripheral organs, and communication across distance; and second, a temporal framework that maps nervous system influence across the operational lifespan of the immune system - specifically focusing on how the nervous system impacts immune cell development, distribution, and execution of functions. Finally, we highlight key tools, clinical applications, and questions for future research on how both systems coordinate to respond to somatic and environmental stressors.
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http://dx.doi.org/10.1038/s41577-025-01199-6 | DOI Listing |
Front Immunol
September 2025
Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Gliomas are the most common primary malignant tumors of the central nervous system (CNS), and despite progress in molecular diagnostics and targeted therapies, their prognosis remains poor. In recent years, immunotherapy has emerged as a promising treatment modality in cancer therapy. However, the inevitable immune evasion by tumor cells is a key barrier affecting therapeutic efficacy.
View Article and Find Full Text PDFBrain Commun
August 2025
Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M6 8FJ, UK.
The cortex of the brain is covered by three meningeal layers: the dura, the arachnoid, and the pia mater. Substantial discoveries have been made demonstrating the structural and functional relationships between these layers, and with other neighbouring structures such as the skull. Importantly, improved understanding of the meningeal lymphatic network places the meninges at the nexus of a cross talk between the brain, peripheral immune system, and the skull bone marrow.
View Article and Find Full Text PDFJ Biochem
September 2025
Division of Enzyme Pathophysiology, Institute for Enzyme Research, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Microglia, the central nervous system's resident macrophages, are critical for immune defense, protecting neurons during infection. Their role in postnatal brain development, particularly after injury, remains unclear. Nucling, a protein up-regulated during cardiac muscle differentiation, regulates NF-κB, influencing apoptosis and cell proliferation.
View Article and Find Full Text PDFNat Rev Cancer
September 2025
Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Neurotoxicity is a common and potentially severe adverse effect from conventional and novel cancer therapy. The mechanisms that underlie clinical symptoms of central and peripheral nervous system injury remain incompletely understood. For conventional cytotoxic chemotherapy or radiotherapy, direct toxicities to brain structures and neurovascular damage may result in myelin degradation and impaired neurogenesis, which eventually translates into delayed neurodegeneration accompanied by cognitive symptoms.
View Article and Find Full Text PDFCell Death Differ
September 2025
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive neurodegeneration. Although current disease-modifying therapies modulate peripheral autoimmune responses, they are insufficient to fully prevent tissue specific neuroinflammation and long-term neuronal and oligodendrocyte loss. Growing evidence implicates various regulated cell death (RCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, not only as downstream consequences of chronic inflammation, but also as active drivers of demyelination, axonal injury, and glial dysfunction in MS.
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