title: Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease.
abstract: Current therapies for autoimmune diseases rely on traditional immunosuppressive medications that expose patients to an increased risk of opportunistic infections and other complications. Immunoregulatory interventions that act prophylactically or therapeutically to induce antigen-specific tolerance might overcome these obstacles. Here we use the transpeptidase sortase to covalently attach disease-associated autoantigens to genetically engineered and to unmodified red blood cells as a means of inducing antigen-specific tolerance. This approach blunts the contribution to immunity of major subsets of immune effector cells (B cells, CD4+and CD8+T cells) in an antigen-specific manner. Transfusion of red blood cells expressing self-antigen epitopes can alleviate and even prevent signs of disease in experimental autoimmune encephalomyelitis, as well as maintain normoglycemia in a mouse model of type 1 diabetes.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
authors.forename: Novalia
authors.initials: N
authors.lastname: Pishesha
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Angelina M
authors.initials: AM
authors.lastname: Bilate
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Marsha C
authors.initials: MC
authors.lastname: Wibowo
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Nai-Jia
authors.initials: NJ
authors.lastname: Huang
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
authors.forename: Zeyang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Rhogerry
authors.initials: R
authors.lastname: Deshycka
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Djenet
authors.initials: D
authors.lastname: Bousbaine
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Hojun
authors.initials: H
authors.lastname: Li
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Heide C
authors.initials: HC
authors.lastname: Patterson
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Dougan
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; lodish@wi.mit.edu hidde.ploegh@childrens.harvard.edu.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Harvey F
authors.initials: HF
authors.lastname: Lodish
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; lodish@wi.mit.edu hidde.ploegh@childrens.harvard.edu.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
keywords: antigen-specific tolerance; autoimmune diseases; engineered red blood cells; sortase