TRI-MPs induce regulatory T cells and donor-specific tolerance in VCA. (A) Schematic illustrating the mechanism of action for Treg-inducing microspheres, where local release of TGFβ1, rapamycin and IL-2 induce Treg conversion from naïve T cells. (B) Effect of TRI-MP treatment on Treg populations in allograft draining inguinal lymph nodes. (C) Impact of TRI-MPs on hindlimb graft survival in a model of vascularized composite allotransplantation (VCA). (D) Increased suppression of TRI-MP treated Tregs on conventional T cell proliferation when stimulated with donor splenocytes when compared to third-party splenocytes. (E) Secondary skin graft challenge demonstrates acceptance of donor skin grafts, but rejection of third-party skin grafts, illustrating the induction of donor-specific tolerance. Data in figures 7B, 7C, 7D and 7E reprinted from J.D. Fisher, S.C. Balmert, W. Zhang, R. Schweizer, J.T. Schnider, C. Komatsu, L. Dong, V.E. Erbas, J.V. Unadkat, A.M. Aral, A.P. Acharya, Y. Kulahci, H.R. Turnquist, A.W. Thomson, M.G. Solari, V.S. Gorantla, S.R. Little, Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation, Proc National Acad Sci. 116 (2019) 25784–25789. https://doi.org/10.1073/pnas.1910701116. Copyright (2021) National Academy of Sciences.