CNS Immune Cell Compartmentalization and Neuroinflammation

Neuroimmunology has demonstrated that T cells residing in the human brain constitute a distinct, tissue-adapted lymphocyte population. Unlike their circulating counterparts, these resident T cells exist within a highly regulated and privileged central nervous system (CNS) environment. A surge in the availability of post-mortem brain tissue, alongside powerful omics and neuroimaging tools, has begun to clarify the unique attributes and behaviors of CNS-resident lymphocytes. In conditions such as multiple sclerosis (MS), there is mounting evidence that these populations do not merely infiltrate the CNS during acute inflammation but occupy specialized niches—most notably within the meninges and perivascular spaces—and interact closely with resident B cells and myeloid cells. Despite advances using both human samples and animal models, fundamental questions remain regarding the precise mechanisms of lymphocyte compartmentalization, their residency programs, and their persistent role in MS pathology, particularly in forms of the disease that resist conventional therapies. Ongoing debates focus on how best to target these cells therapeutically, especially given their contribution to progressive and compartmentalized neuroinflammation.This Research Topic aims to serve as a platform for innovative studies elucidating the mechanisms of lymphocyte recruitment, maintenance, and interaction within the human brain, with an emphasis on their relevance to multiple sclerosis and other neuroinflammatory or neurodegenerative disorders. Specifically, it seeks to integrate data across translational models—spanning human studies, animal experiments, and clinical trial analysis to address how T cells and other lymphocytes are sequestered in CNS niches, how these populations evolve during disease progression, and how local microenvironments influence their behavior and persistence. By bridging basic and translational research, this endeavor aspires to fuel the development of novel therapies capable of targeting compartmentalized immune processes central to progressive MS.The Scope of this Research Topic encompasses fundamental and translational studies focused on lymphocyte dynamics at CNS borders in health and disease but excludes purely descriptive or non-mechanistic accounts. We expressly invite research that integrates molecular, cellular, imaging, or clinical perspectives to deepen understanding of compartmentalized neuroimmunity. To gather further insights in these areas, we welcome articles addressing, but not limited to, the following themes:• Mechanisms of T cell and B cell recruitment to, and retention within, CNS compartments• The role of border-associated macrophages, microglia, and resident myeloid populations in lymphocyte maintenance and function• Distinct residency programs of lymphocytes within perivascular and meningeal niches• Innovative imaging approaches (MRI/PET) correlating immune cell distribution with clinical and pathological outcomes• Translational analyses linking clinical trial data to cellular compartmentalization and disease progression in MS Topic editors: Joost Smolders, Jörg Hamann Source: https://www.frontiersin.org/research-topics/79644/cns-immune-cell-compartmentalization-and-neuroinflammation