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Here, we developed trackable tolerogenic macrophages (\n                    <jats:bold>TTMs<\/jats:bold>\n                    ), engineered to overexpress PD\u2010L1, incorporate azide groups for bioorthogonal labeling, and encapsulate rapamycin nanoparticles (RAPA NPs). Following intravenous administration in murine allografts,\n                    <jats:bold>TTMs<\/jats:bold>\n                    preferentially homed to inflamed grafts and were visualized in vivo.\n                    <jats:bold>TTMs<\/jats:bold>\n                    reduced graft inflammation and prolonged allograft survival up to 35 days, significantly longer than PD\u2010L1 or RAPA monotherapy groups. Mechanistic studies showed that PD\u2010L1 ligation of PD\u20101 suppressed Th1 differentiation and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell activation, reducing IFN\u2010\u03b3\/TNF\u2010\u03b1 and thereby attenuating complement activation and PI3K\/Akt\/mTOR signaling. This enhanced rapamycin\u2010mediated mTOR inhibition and promoted Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Treg induction with increased IL\u201010 production. The elevated IL\u201010 further strengthened PD\u20101\/PD\u2010L1 signaling, forming a feedback loop that maintained a tolerogenic microenvironment. Together, these findings highlight\n                    <jats:bold>TTMs<\/jats:bold>\n                    as multifunctional therapeutic cells that integrate graft homing, real\u2010time tracking, and dual\u2010pathway immunoregulation to advance precision immunotherapy in transplantation.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520420","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T17:37:57Z","timestamp":1770572277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Trackable Tolerogenic Macrophages Integrate PD\u2010L1 and Rapamycin Signaling to Suppress Alloimmune Responses in Transplantation"],"prefix":"10.1002","volume":"13","author":[{"given":"Yihui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ultrasound Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Clinical 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