Helminth egg derivatives as proregenerative immunotherapies

David R. Maestas; Liam Chung; Jin Han; Xiaokun Wang; Sven D. Sommerfeld; Sean H. Kelly; Erika Moore; Helen Hieu Nguyen; Joscelyn C. Mejías; Alexis N. Peña; Hong Zhang; Joshua S.T. Hooks; Alexander F. Chin; James I. Andorko; Cynthia A. Berlinicke; Kavita Krishnan; Younghwan Choi; Amy E. Anderson; Ronak Mahatme; Christopher Mejia; Marie Eric; Ji Won Woo; Sudipto Ganguly; Donald J. Zack; Liang Zhao; Edward J. Pearce; Franck Housseau; Drew M. Pardoll; Jennifer H. Elisseeff

doi:10.1073/pnas.2211703120

Helminth egg derivatives as proregenerative immunotherapies

David R. Maestas, Liam Chung, Jin Han, Xiaokun Wang, Sven D. Sommerfeld, Sean H. Kelly, Erika Moore, Helen Hieu Nguyen, Joscelyn C. Mejías, Alexis N. Peña, Hong Zhang, Joshua S.T. Hooks, Alexander F. Chin, James I. Andorko, Cynthia A. Berlinicke, Kavita Krishnan, Younghwan Choi, Amy E. Anderson, Ronak Mahatme, Christopher MejiaMarie Eric, Ji Won Woo, Sudipto Ganguly, Donald J. Zack, Liang Zhao, Edward J. Pearce, Franck Housseau, Drew M. Pardoll, Jennifer H. Elisseeff

School of Medicine

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

Abstract

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.

Original language	English (US)
Article number	e2211703120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Issue number	8
DOIs	https://doi.org/10.1073/pnas.2211703120
State	Published - Feb 21 2023

Keywords

biomaterials
helminth
immune response
regenerative medicine
tissue engineering

ASJC Scopus subject areas

General

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10.1073/pnas.2211703120

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Maestas, D. R., Chung, L., Han, J., Wang, X., Sommerfeld, S. D., Kelly, S. H., Moore, E., Nguyen, H. H., Mejías, J. C., Peña, A. N., Zhang, H., Hooks, J. S. T., Chin, A. F., Andorko, J. I., Berlinicke, C. A., Krishnan, K., Choi, Y., Anderson, A. E., Mahatme, R., ... Elisseeff, J. H. (2023). Helminth egg derivatives as proregenerative immunotherapies. Proceedings of the National Academy of Sciences of the United States of America, 120(8), Article e2211703120. https://doi.org/10.1073/pnas.2211703120

Maestas, DR, Chung, L, Han, J, Wang, X, Sommerfeld, SD, Kelly, SH, Moore, E, Nguyen, HH, Mejías, JC, Peña, AN, Zhang, H, Hooks, JST, Chin, AF, Andorko, JI, Berlinicke, CA, Krishnan, K, Choi, Y, Anderson, AE, Mahatme, R, Mejia, C, Eric, M, Woo, JW, Ganguly, S, Zack, DJ, Zhao, L, Pearce, EJ , Housseau, F , Pardoll, DM & Elisseeff, JH 2023, 'Helminth egg derivatives as proregenerative immunotherapies', Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 8, e2211703120. https://doi.org/10.1073/pnas.2211703120

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title = "Helminth egg derivatives as proregenerative immunotherapies",

abstract = "The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.",

keywords = "biomaterials, helminth, immune response, regenerative medicine, tissue engineering",

author = "Maestas, {David R.} and Liam Chung and Jin Han and Xiaokun Wang and Sommerfeld, {Sven D.} and Kelly, {Sean H.} and Erika Moore and Nguyen, {Helen Hieu} and Mej{\'i}as, {Joscelyn C.} and Pe{\~n}a, {Alexis N.} and Hong Zhang and Hooks, {Joshua S.T.} and Chin, {Alexander F.} and Andorko, {James I.} and Berlinicke, {Cynthia A.} and Kavita Krishnan and Younghwan Choi and Anderson, {Amy E.} and Ronak Mahatme and Christopher Mejia and Marie Eric and Woo, {Ji Won} and Sudipto Ganguly and Zack, {Donald J.} and Liang Zhao and Pearce, {Edward J.} and Franck Housseau and Pardoll, {Drew M.} and Elisseeff, {Jennifer H.}",

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AU - Maestas, David R.

AU - Chung, Liam

AU - Han, Jin

AU - Wang, Xiaokun

AU - Sommerfeld, Sven D.

AU - Kelly, Sean H.

AU - Moore, Erika

AU - Nguyen, Helen Hieu

AU - Mejías, Joscelyn C.

AU - Peña, Alexis N.

AU - Zhang, Hong

AU - Hooks, Joshua S.T.

AU - Chin, Alexander F.

AU - Andorko, James I.

AU - Berlinicke, Cynthia A.

AU - Krishnan, Kavita

AU - Choi, Younghwan

AU - Anderson, Amy E.

AU - Mahatme, Ronak

AU - Mejia, Christopher

AU - Eric, Marie

AU - Woo, Ji Won

AU - Ganguly, Sudipto

AU - Zack, Donald J.

AU - Zhao, Liang

AU - Pearce, Edward J.

AU - Housseau, Franck

AU - Pardoll, Drew M.

AU - Elisseeff, Jennifer H.

PY - 2023/2/21

Y1 - 2023/2/21

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KW - immune response

KW - regenerative medicine

KW - tissue engineering

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Helminth egg derivatives as proregenerative immunotherapies

Abstract

Keywords

ASJC Scopus subject areas

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