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The emergence of nanogenerators offers a promising avenue to overcome these obstacles, introducing a new paradigm for regulating neural immune responses. This review delves into the complex physiological landscape of neuroimmunity, emphasizing its profound impact on overall health and disease outcomes. It systematically examines the mechanisms by which nanogenerators interact with and modulate neuroimmune processes, while also charting key developmental milestones, synthesis strategies, and classification frameworks of nanogenerators. Particular attention is given to the application of nanogenerators in neuroimmunomodulation, critically analyzing current achievements, persistent challenges, and future directions. Furthermore, the review highlights the potential clinical translation of nanogenerators, notably their capacity to stimulate the vagus nerve and activate the brain's immune system, offering innovative therapeutic strategies for a spectrum of neurological disorders, including epilepsy, PD, AD, and stroke. As we navigate the ethereal tightrope of immune homeostasis, nanogenerators emerge as beacons of hope, heralding a future in which precise, targeted modulation of neuroimmunity may evolve from conceptual possibility to clinical reality.<\/jats:p>","DOI":"10.1002\/advs.202512284","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T19:37:31Z","timestamp":1770665851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Navigating the Ethereal Tightrope: The Nanogenerator Manipulates Neurons for Immune Equilibrium"],"prefix":"10.1002","volume":"13","author":[{"given":"Jia","family":"Du","sequence":"first","affiliation":[{"name":"Department of Haematology Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital School of Medicine of University of Electronic Science and Technology of China  Chengdu 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