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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Article numbere2211703120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number8
DOIs
StatePublished - Feb 21 2023

Keywords

  • biomaterials
  • helminth
  • immune response
  • regenerative medicine
  • tissue engineering

ASJC Scopus subject areas

  • General

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