biostudies-literatureMaestas DRHHS | National Institutes of HealthNEI NIH HHSNCATS NIH HHSNIA NIH HHSNIAID NIH HHSU.S. Department of DefenseNCI NIH HHSNIAMS NIH HHSHHS | NIH | National Eye Institutee2211703120https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974432biostudies-literatureUnknown120(8)The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth <i>Schistosoma mansoni</i> 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 joProceedings of the National Academy of Sciences of the United States of AmericaHelminth egg derivatives as proregenerative immunotherapies.PMC9974432DP1 AR076959DP1AR076959T32 CA153952HHSN272201700014CKL2 TR001429W81XWH-19-1-0576R01 EY029055T32 AG058527R01EY029055Elisseeff JHPearce EJPena ANGanguly SZhang HZack DJMejia CSommerfeld SDNguyen HHAnderson AEZhao LKelly SHAndorko JIHousseau FChoi YWang XWoo JEric MChung LChin AFMejias JCHooks JSTMaestas DRKrishnan KMahatme RHan JBerlinicke CAMoore EPardoll DMfalseHelminth egg derivatives as proregenerative immunotherapies.The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth <i>Schistosoma mansoni</i> 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 jo2023-01-01T00:00:00Z2023 Feb2025-04-04T22:55:13.261Z2025-04-04T22:55:13.261ZS-EPMC99744323678052210.1073/pnas.2211703120