Helminth egg derivatives as pro-regenerative immunotherapies

Maestas, D. R.; Chung, L.; Han, J.; Wang, X.; Sommerfeld, S. D.; Moore, E.; Hieu Nguyen, H.; Mejias, J. C.; Pena, A. N.; Zhang, H.; Hooks, J. S. T.; Chin, A. F.; Andorko, J. I.; Berlicke, C.; Krishnan, K.; Choi, Y.; Anderson, A. E.; Mahatme, R.; Mejia, C.; Eric, M.; Woo, J.; Ganguly, S.; Zack, D. J.; Housseau, F.; Pardoll, D. M.; Elisseeff, J. H.

doi:10.1101/2022.05.02.490277

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bioRxiv · 10.1101/2022.05.02.490277

Helminth egg derivatives as pro-regenerative immunotherapies

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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 ({gamma}{delta}) 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 new regenerative immunotherapy approach using natural helminth-derivatives. One-Sentence SummaryHelminth-derived soluble egg antigen regenerative immunotherapies promote tissue repair in multiple injury models.

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Maestas, D. R., Chung, L., Han, J., Wang, X., Sommerfeld, S. D., Moore, E., Hieu Nguyen, H., Mejias, J. C., Pena, A. N., Zhang, H., Hooks, J. S. T., Chin, A. F., Andorko, J. I., Berlicke, C., Krishnan, K., Choi, Y., Anderson, A. E., Mahatme, R., Mejia, C., Eric, M., Woo, J., Ganguly, S., Zack, D. J., Housseau, F., Pardoll, D. M., Elisseeff, J. H.. 2022-05-04. Helminth egg derivatives as pro-regenerative immunotherapies. https://doi.org/10.1101/2022.05.02.490277

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