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Cell therapy is expected to replace immunosuppressive agents. However, while Treg cell therapy can mitigate immune rejection, it fails to significantly prolong graft survival because peripherally induced Treg cells exhibit transdifferentiation potential in the circulatory system. Recent advances in nanocarrier systems offer promising approaches for achieving graft\u2010specific immune tolerance. Through single\u2010cell sequencing analysis, CD248 is identified as a pivotal stromal cell marker in renal allograft rejection, modulated by HIF\u20101\u03b1 and IL\u20101\u03b2 signaling pathways. Leveraging macrophage membrane coating technology, nanoparticles co\u2010loaded is developed with IL\u20102 and TGF\u2010\u03b2 expressing plasmids. These nanoparticles incorporate a CD248\u2010targeting antibody (IgG78) and plasmids containing a kidney\u2010specific NPHS2 promoter, enabling dual\u2010targeting capability for localized gene expression. In vitro validation demonstrated efficient differentiation of CD4\u207aT cells into functional Treg populations. In rat renal transplantation models, nanoparticle treatment increased Treg cells in the graft and significantly prolonged allograft survival, improved renal function, and attenuated complement deposition. The findings establish a targeted nanoparticle platform that promotes graft\u2010specific immune tolerance through localized Treg cell expansion, potentially reducing dependence on systemic immunosuppression.<\/jats:p>","DOI":"10.1002\/advs.202507943","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T11:15:21Z","timestamp":1761304521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted Expansion of Treg Cells to Induce Immune Tolerance after Kidney Transplantation"],"prefix":"10.1002","volume":"13","author":[{"given":"Tong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Urology Xijing Hospital Fourth Military Medical University  Xi'an 710032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology Xijing Hospital Fourth Military Medical 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