Helminth egg derivatives as proregenerative immunotherapies
David R. Maestas, Liam Chung, Jin Han, Xiaokun Wang, Sven D. Sommerfeld, Sean H. Kelly, Erika Moore, Helen Nguyễn, Joscelyn C. Mejías, Alexis N. Peña, Hong Zhang, Joshua S. T. Hooks, Alexander F. Chin, James I. Andorko, Cynthia Berlinicke, Kavita Krishnan, Tae Hyun Choi, Amy E. Anderson, Ronak J. Mahatme, Christopher Mejia, Marie Eric, J. Woo, Sudipto Ganguly, Donald J. Zack, Liang Zhao, Edward J. Pearce, Franck Housseau, Drew M. Pardoll, Jennifer H. Elisseeff
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-4-expressing 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.