@article{c03db7bf143246a792074f44362d350c,
title = "In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation",
abstract = "Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection. To achieve donor-specific immune tolerance and reduce the need for systemic immunosuppression, we developed a synthetic drug delivery system that mimics a strategy our bodies naturally use to recruit regulatory T cells (Treg) to suppress inflammation. Specifically, a microparticle-based system engineered to release the Treg-recruiting chemokine CCL22 was used in a rodent hindlimb VCA model. These “Recruitment-MP” prolonged hindlimb allograft survival indefinitely (>200 days) and promoted donor-specific tolerance. Recruitment-MP treatment enriched Treg populations in allograft skin and draining lymph nodes and enhanced Treg function without affecting the proliferative capacity of conventional T cells. With implications for clinical translation, synthetic human CCL22 induced preferential migration of human Treg in vitro. Collectively, these results suggest that Recruitment-MP promote donor-specific immune tolerance via local enrichment of suppressive Treg.",
author = "Fisher, {James D.} and Wensheng Zhang and Balmert, {Stephen C.} and Aral, {Ali M.} and Acharya, {Abhinav P.} and Yalcin Kulahci and Jingjing Li and Turnquist, {Heth R.} and Thomson, {Angus W.} and Solari, {Mario G.} and Gorantla, {Vijay S.} and Little, {Steven R.}",
note = "Funding Information: Flow cytometry analyses and FACS sorting were conducted at the University of Pittsburgh's Unified Flow Core and benefitted from a Special BD LSR Fortessa funded by the NIH (1-S10-OD011925-01). We thank A. MacIntyre and D. Falkner for assistance with FACS sorting. Histological services were provided by the McGowan Institute for Regenerative Medicine Histology Core. This research was funded by the NIH NIAID (R01-AI118777 and U19-AI131453 to A.W.T. and R01-HL122489 to H.R.T.), NIH NIDCR (R01-DE021058 to S.R.L.), DoD CDMRP (W81XWH-15-2-0027 to A.W.T. and W81XWH-15-1-0244 to S.R.L. and V.S.G.), and the Camille and Henry Dreyfus Foundation (to S.R.L.). J.D.F. was supported by a fellowship from the NIH NIAID (T32-AI074490), and SCB was supported by a fellowship from the NIH NCI (T32-CA175294). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2020",
doi = "10.1126/sciadv.aax8429",
language = "English (US)",
volume = "6",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "11",
}