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A key obstacle to restoring immune homeostasis lies in the reciprocal reinforcement between endothelial\u2010to\u2010mesenchymal transition (EndMT) and sustained immune infiltration, which collectively exacerbate blood\u2013brain barrier (BBB) disruption and neuroinflammation. We identified IL7R as a shared target on endothelial cells and pathogenic T cells via scRNA\u2010seq and developed a multifunctional nanodelivery platform\u2014\n                    <jats:italic>ETS1<\/jats:italic>\n                    pDNA\/PBAE@ITP\u2010MM (IMNP)\u2014comprising\n                    <jats:italic>ETS1<\/jats:italic>\n                    plasmid DNA complexed with poly(\u03b2\u2010amino ester) (PBAE), an interleukin\u20107 receptor (IL7R)\u2010targeting peptide (ITP), and a macrophage membrane (MM) coating. IMNP concurrently modulates endothelial cells and T lymphocytes for synergistic efficacy. Exploiting the intrinsic inflammation\u2010targeting capacity of activated macrophage membranes and ITP conjugation, IMNPs preferentially accumulate at the vascular endothelium, where they inhibit EndMT and preserve BBB integrity. Subsequently, IMNPs attenuate differentiation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells into proinflammatory Th1\/Th17 subsets, thereby reducing CNS infiltration and re\u2010establishing immune microenvironmental balance in both relapsing\u2010remitting MS (RRMS) and secondary progressive MS (SPMS) models. Our findings provide proof\u2010of\u2010concept for a biomimetic nanoplatform that achieves dual vascular\u2010immune modulation, significantly alleviating neuroinflammation, reducing demyelination, and improving motor performance in both RRMS and SPMS models.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504951","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T13:14:24Z","timestamp":1769519664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered ETS1\u2010Nanoconjugate Restores Immune Homeostasis through Dual Immune\u2010Vascular Modulation in Relapsing and Progressive Multiple Sclerosis"],"prefix":"10.1002","volume":"15","author":[{"given":"Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 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