Helminth egg derivatives as proregenerative immunotherapies

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 8; p. e2211703120
• Main Authors: Maestas, Jr, David R, Chung, Liam, Han, Jin, Wang, Xiaokun, Sommerfeld, Sven D, Kelly, Sean H, Moore, Erika, Nguyen, Helen Hieu, Mejías, Joscelyn C, Peña, Alexis N, Zhang, Hong, Hooks, Joshua S T, Chin, Alexander F, Andorko, James I, Berlinicke, Cynthia A, Krishnan, Kavita, Choi, Younghwan, Anderson, Amy E, Mahatme, Ronak, Mejia, Christopher, Eric, Marie, Woo, JiWon, Ganguly, Sudipto, Zack, Donald J, Zhao, Liang, Pearce, Edward J, Housseau, Franck, Pardoll, Drew M, Elisseeff, Jennifer H
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 21-02-2023
• Subjects: Animals; Antigens; Antigens, Helminth; Biological Sciences; Complications; Controlled release; Cornea; Cytokines - metabolism; Eggs; Eosinophils; Fibrosis; Helper cells; Hydrogels; Immune system; Immunoregulation; Immunotherapy; Interleukin 4; Leukocytes (eosinophilic); Lymphocytes; Lymphocytes T; Mice; Muscles; Schistosoma mansoni; Schistosomiasis mansoni - therapy; Soluble egg antigen; T-Lymphocytes, Helper-Inducer; tissue engineering; biomaterials; helminth; immune response; regenerative medicine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2211703120

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth
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.