This Research Topic is the fourth volume of the “Trends in Neuroimmunology: cross-talk between brain-resident and peripheral immune cells in both health and disease” Community Series. Please see Volumes I here, II here, and III here for previous contributions.

The functional anatomy of organisms is maintained by the coordination of different systems, that often rely on interactions between specialized cells and between macromolecules. The immune system works with the circulatory and the lymphatic systems to protect most of the organs. However, some organs are considered immune privileged due to the presence of highly selective and regulated barriers, such as the blood-brain barrier (BBB) within the brain. The BBB controls periphery-brain molecule exchange and prevents immune effector cells from entering the homeostatic brain. BBB-associated elements, such as endothelial cells, pericytes, astrocytes, and microglia, potentially can function as antigen-presenting cells (APC).

Pathological scenarios that induce dysfunction of the BBB and its associated cells may lead to the infiltration of lymphocytes crossing over from the blood to brain. Similarly, traumas can also enable B and T lymphocytes to pass bidirectionally between the CNS and the periphery, via the meningeal lymphatic vessels which drain into the cervical lymph nodes.

Research in animals and in humans has revealed that B and T cells are involved in the progression of neurological diseases. It has been shown that under certain conditions, T cells establish themselves and become resident in the brain (TRM cells), from where they can either exert beneficial or detrimental effects on brain function. Amazing efforts have been made to further comprehend interactions between brain specific cells and peripheral immune cells, and especially their roles and impact on the onset, progression, and eventual resolution of diverse brain pathologies.

This proposed Research Topic will describe our current understanding of CNS-specific immune responsiveness in both health and disease. It will cover the interrelationship between brain specific and peripheral immunity, mechanisms for maintaining brain homeostasis, and responses to insults such as tumors, neuroinflammation, cerebrovascular diseases and stroke, neuropsychiatric and neurodevelopmental disorders, and neurodegenerative and autoimmune diseases.

The proposed Research Topic will especially focus on microglia’s role in neuroimmunology, but will not be limited to this cell type. Related topics include:

• Participation of microglia, T cells, B cells, monocytes and macrophages in maintaining CNS homeostasis;

• Cross-talk between brain-resident and peripheral immune cells at cellular and molecular levels in diverse brain pathologies;

• Structural and functional dynamics of immune cells coupled to milieu changes within the CNS;

• Establishment and integrity of the BBB and its involvement in peripheral immune cell recruitment in neuroinflammatory and neurodegenerative scenarios;

• Participation of circumventricular organs (CVOs), the glymphatic system, and brain border niches in periphery-CNS immune interactions;

• Sex-dependent and age-dependent differences in neuroimmune responses, including immune senescence;

• Neuroinflammatory consequences of systemic infections and post-infectious syndromes;

• Extracellular vesicles and secreted factors as mediators of neuro-immune communication;

• Identification of genes, pathways, and biomarkers for therapeutic intervention in neuroinflammation and neurodegeneration;

• Development of model organisms for studying brain immunity in health and disease;

• State-of-art technologies, including spatial transcriptomics, single-cell and single-nucleus approaches, multi-omics integration, and artificial intelligence-assisted analysis, applied to immune responses within the nervous system;

• Diagnostic and therapeutic immune-based approaches in the CNS context, including immunotherapy and cell-based therapies.

Original articles, reviews and short communications are welcome. We expect to attract significant contributions from diverse specialists in the field, to establish new trends for future studies.

Are you interested in contributing a manuscript to this Research Topic?

Community Series in Trends in Neuroimmunology: cross-talk between brain-resident and peripheral immune cells in both health and disease, volume IV