title: Engineering an "infectious" T(reg) biomimetic through chemoselective tethering of TGF-β1 to PEG brush surfaces.
abstract: Modulation of immunological responses to allografts following transplantation is of pivotal importance to improving graft outcome and duration. Of the many approaches, harnessing the dominant tolerance induced by regulatory T cells (Treg) holds tremendous promise. Recent studies have highlighted the unique potency of cell surface-bound TGF-β1 on Treg for promoting infectious tolerance, i.e. to confer suppressive capacity from one cell to another. To mimic this characteristic, TGF-β1 was chemoselectively tethered to inert and viable polymer grafting platforms using Staudinger ligation. We report the synthesis and functional characterization of these engineered TGF-β1 surfaces. Inert beads tethered with TGF-β1 were capable of efficiently converting naïve CD4(+) CD62L(hi) T cells to functional Treg. Concordantly, translation of conjugation scheme from inert surfaces to viable cells also led to efficient generation of functional Treg. Further, the capacity of these platforms to generate antigen-specific Treg was demonstrated. These findings illustrate the unique faculty of tethered TGF-β1 biomaterial platforms to function as an "infectious" Treg and provide a compelling approach for generating tolerogenic microenvironments for allograft transplantation.
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Yang
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Medicine, University of Miami, Miami, FL, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Kronenfeld
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Gattás-Asfura
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Microbiology and Immunology, University of Miami, Miami, FL, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Bayer
authors.affiliation: Diabetes Research Institute, University of Miami, Miami, FL, USA; Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA; Department of Biomedical Engineering, University of Miami, Miami, FL, USA; Department of Surgery, University of Miami, Miami, FL, USA. Electronic address: cstabler@bme.ufl.edu.
authors.forename: C L
authors.initials: CL
authors.lastname: Stabler
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008422:Materials Testing / Q000379:methods*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008863:Microspheres; D010795:Phthalic Acids / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D010795:Phthalic Acids; D053773:Transforming Growth Factor beta1; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; C011363:terephthalic acid
keywords: Biomaterials; Immunomodulation; Regulatory T cells; Staudinger ligation