Helminth egg derivatives as proregenerative immunotherapies.
David R MaestasLiam ChungJin HanXiaokun WangSven D SommerfeldSean H KellyErika M MooreHelen Hieu NguyenJoscelyn C MejíasAlexis N PeñaHong ZhangJoshua S T HooksAlexander F ChinJames I AndorkoCynthia A BerlinickeKavita KrishnanYounghwan ChoiAmy E AndersonRonak MahatmeChristopher MejiaMarie EricJiWon WooSudipto GangulyDonald J ZackLiang ZhaoEdward J PearceFranck HousseauDrew M PardollJennifer H ElisseeffPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
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.
Keyphrases
- regulatory t cells
- stem cells
- tissue engineering
- mesenchymal stem cells
- cell therapy
- dendritic cells
- induced apoptosis
- drug delivery
- skeletal muscle
- wound healing
- high glucose
- bone marrow
- transcription factor
- optical coherence tomography
- immune response
- endothelial cells
- oxidative stress
- signaling pathway
- drug induced
- binding protein
- endoplasmic reticulum stress
- pi k akt
- stress induced