This comprehensive review explores the evolving understanding of the central nervous system (CNS) and its intricate relationship with the immune system, challenging the long-held concept of CNS immune privilege. It highlights the crucial roles of the glymphatic system, which clears waste from the brain, and meningeal lymphatic vessels, which drain antigens to the periphery, in maintaining brain-immune dialogue. The text further discusses how inflammation, aging, and neurodegenerative diseases like Alzheimer's disrupt this delicate balance, leading to an "altered immune code" that can contribute to autoimmunity and impaired cognitive function. Ultimately, the article proposes that deciphering this immune code offers promising avenues for developing novel therapeutic strategies for various CNS pathologies.

References:

• Kim M W, Kipnis J. Glymphatics and meningeal lymphatics unlock the brain-immune code[J]. Immunity, 2025, 58(5): 1040-1051.

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