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As a nuclear\u2010stored alarmin protein, IL\u201033 is released under cell stress or damage, triggering immune responses through its receptor complex, composed of ST2L and the IL\u20101 receptor accessory protein (IL\u20101RAcP). The receptors for IL\u201033 are expressed in various cell types within the nervous system, including neurons, astrocytes, and microglia, and play a crucial role in neurodevelopment and the pathogenesis of neurological diseases. In neurodevelopment, IL\u201033 promotes microglial metabolic adaptation and phagocytosis via the IL\u201033\/ST2\/Akt axis, modulates glial function to affect neural circuit maturation, and influences oligodendrocyte differentiation. In neurological disorders, IL\u201033 exerts context\u2010dependent regulatory effects in the nervous system through modulation of myeloid and T\u2010cell responses, maintenance of barrier integrity, promotion of tissue repair, and regulation of neuroimmune homeostasis. In acute CNS injuries such as ischemic stroke and traumatic brain injury, IL\u201033 is generally associated with anti\u2010inflammatory polarization and enhanced repair, although circulating levels may also reflect injury severity. In chronic neurodegenerative diseases including Alzheimer's and Parkinson's disease, IL\u201033 is implicated in amyloid\u2010\u03b2 clearance, remyelination, glymphatic function, and neuroprotection, while dysregulation of the IL\u201033\/sST2 axis correlates with disease progression. In contrast, IL\u201033 may facilitate tumor progression in glioma. Emerging evidence also supports IL\u201033 and sST2 as potential biomarkers for diagnosis and prognosis in CNS disorders.<\/jats:p>","DOI":"10.1111\/imcb.70138","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:10:01Z","timestamp":1781244601000},"page":"671-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of the IL\u201033\/ST2 Axis in Nervous System Development and Diseases"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2769-5706","authenticated-orcid":false,"given":"Zhoutong","family":"Luo","sequence":"first","affiliation":[{"name":"First School of Clinical Medicine Guangdong Pharmaceutical University  Guangzhou Guangdong 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