Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease

Novalia Pishesha, Angelina M. Bilate, Marsha C. Wibowo, Nai Jia Huang, Zeyang Li, Rhogerry Dhesycka, Djenet Bousbaine, Hojun Li, Heide C. Patterson, Stephanie K. Dougan, Takeshi Maruyama, Harvey F. Lodish, Hidde L. Ploegh

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 diseaseassociated 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 antigenspecific 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.

Original languageEnglish
Pages (from-to)3157-3162
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number12
DOIs
Publication statusPublished - 2017 Mar 21
Externally publishedYes

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Keywords

  • Antigen-specific tolerance
  • Autoimmune diseases
  • Engineered red blood cells
  • Sortase

ASJC Scopus subject areas

  • General

Cite this

Pishesha, N., Bilate, A. M., Wibowo, M. C., Huang, N. J., Li, Z., Dhesycka, R., Bousbaine, D., Li, H., Patterson, H. C., Dougan, S. K., Maruyama, T., Lodish, H. F., & Ploegh, H. L. (2017). Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease. Proceedings of the National Academy of Sciences of the United States of America, 114(12), 3157-3162. https://doi.org/10.1073/pnas.1701746114