In:
Science, American Association for the Advancement of Science (AAAS), Vol. 380, No. 6640 ( 2023-04-07)
Abstract:
Beginning in the early 19th century, the brain was considered a self-contained organ behind barriers and thus as “immune privileged.” This assumption was supported by experiments showing that a dye injected into the circulation did not stain the brain and by evidence of prolonged survival of tissue grafts in the brain compared with transplants into peripheral tissues. These conclusions led to the axiomatic view that the brain cannot tolerate any immune activity. The identification of brain-resident immune cells, the microglia, was often used as an additional argument to support the immunological self-sufficiency of the brain. In addition, despite the early description of brain lymphatic drainage, which dates back to 1787, the supposed absence of lymphatic vessels within the brain was, until recently, among the most common rationales used to support the view of a complete separation between the brain and the immune system. ADVANCES Our perception of the relationship between the brain and the immune system has completely changed over the past decades. It is now established that immune cells operate as guardians of the central nervous system (CNS), support brain function and repair, and reside in specialized immunological niches at its borders, including the meninges, the choroid plexus, and the perivascular spaces. The meninges remotely affect the brain through immune cell–derived cytokine release. The choroid plexus hosts and orchestrates the selective homing of immune cells to the CNS parenchyma. The perivascular spaces are populated by immune cells regulating cerebrospinal fluid flow. The demonstration of the CNS lymphatic system and brain drainage led to the identification of the brain-draining cervical lymph nodes as crucial supplementary sites of the interaction between the CNS and the immune system. Additional observations revealed that microscopic channels in the bone of the skull allow exposure of the bone marrow (BM) to the cerebrospinal fluid, thereby influencing cellular maturation in the BM and migration into the brain. Such an intricate communication network guarantees efficient CNS-monitoring activities by neighboring immune cells, the phenotype of which is shaped by the CNS microenvironment to which they are constantly exposed. The bidirectional nature of the CNS–immune system interplay is supported by emerging studies demonstrating the ability of neuronal cells to modulate the immune response through lymphoid organ innervation in the context of CNS diseases. OUTLOOK The negative side of the immune system participating in brain physiology is that imbalanced brain-immune interactions might be critical in aging and in autoimmune, neurodegenerative, and neurodevelopmental disorders. Under such conditions, the perturbed brain microenvironment might lead to a harmful immune response, which may exacerbate disease manifestations. Further advances in our understanding of brain immunity and the reciprocal ability of the CNS and the immune system to sense and influence each other will offer intervention tools for the design of new therapeutic strategies for treating brain pathologies. Understanding what goes awry in each of the brain’s immune niches, including the skull BM, the meninges, and the choroid plexus, as well as in lymphatic drainage, might reveal new potential targets for therapeutic approaches in the near future. New perception of brain immunity. Shown is a representation of the communication network allowing fine-tuned brain immunosurveillance. The immune cells are strategically positioned in immunological niches, where they are constantly exposed to CNS cues transported by the intracranial interstitial, cerebrospinal, and lymphatic fluid. Upon sensing brain signals, the immune cells can migrate toward the CNS to exert their effector functions.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.abo7649
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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