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

doi:10.1073/pnas.1701746114

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

111 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 language	English
Pages (from-to)	3157-3162
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	12
DOIs	https://doi.org/10.1073/pnas.1701746114
Publication status	Published - 2017 Mar 21
Externally published	Yes

Keywords

Antigen-specific tolerance
Autoimmune diseases
Engineered red blood cells
Sortase

ASJC Scopus subject areas

General

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10.1073/pnas.1701746114

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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

Pishesha, N, Bilate, AM, Wibowo, MC, Huang, NJ, Li, Z, Dhesycka, R, Bousbaine, D, Li, H, Patterson, HC, Dougan, SK, Maruyama, T, Lodish, HF & Ploegh, HL 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, vol. 114, no. 12, pp. 3157-3162. https://doi.org/10.1073/pnas.1701746114

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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 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. ",

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doi = "10.1073/pnas.1701746114",

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AU - Bilate, Angelina M.

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AU - Huang, Nai Jia

AU - Li, Zeyang

AU - Dhesycka, Rhogerry

AU - Bousbaine, Djenet

AU - Li, Hojun

AU - Patterson, Heide C.

AU - Dougan, Stephanie K.

AU - Maruyama, Takeshi

AU - Lodish, Harvey F.

AU - Ploegh, Hidde L.

PY - 2017/3/21

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AB - 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.

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

Abstract

Keywords

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