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Interleukin\u20103 (IL\u20103), a significant regulatory factor, has been involved in the pathogenesis of various diseases, yet its effects on neuroinflammation post\u2010TBI through microglia remain unclear. Here, we evaluate the potential of IL\u20103 to alleviate neuroinflammation in microglia following TBI. Using the ABplex Multi\u2010Metric Streaming Joint Analysis to detect inflammatory factors, we observed significantly elevated levels of IL\u20103 in cerebrospinal fluid, but not in blood samples, of patients with headaches and TBI. In addition, we found that administration of exogenous IL\u20103 within the brain reduced neuroinflammation and promoted functional recovery in rat TBI models. Mechanistically, we identified Peroxiredoxin\u20101 (PRDX1) as the target of IL\u20103 in microglia. Notably, the protective effects of IL\u20103 in TBI rats were abolished when PRDX1 was specifically knocked down in microglia. In conclusion, our experimental research demonstrates that IL\u20103 acts as a key modulator via regulating microglia polarization to inhibit neuroinflammation. IL\u20103 improves neurological function and prognosis in TBI rats by recruiting PRDX1 through IL\u20103R to modulate microglia polarization. Therefore, IL\u20103 may represent a novel therapeutic strategy for TBI.<\/jats:p>","DOI":"10.1002\/advs.202504511","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:51:19Z","timestamp":1774986679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL\u20103 Modulates Microglia Polarization and Attenuates Neuroinflammation in Traumatic Brain Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Nana","family":"Huang","sequence":"first","affiliation":[{"name":"Central Hospital Affiliated to Shandong First Medical University Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan China"},{"name":"Jinan Central Hospital Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Central Hospital Affiliated to Shandong First Medical 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