Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD 21287.
Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, School of Medicine, Baltimore, MD 21287.
Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2211703120. doi: 10.1073/pnas.2211703120. Epub 2023 Feb 13.
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.
免疫系统越来越被认为是组织修复的重要调节剂。我们从寄生虫可溶性卵抗原(SEA)中开发了一种再生免疫疗法,以刺激白细胞介素(IL)-4 和其他 2 型相关细胞因子的产生,而不会产生负面的感染相关后遗症。将再生 SEA(rSEA)应用于小鼠肌肉损伤可诱导表达 IL-4 的辅助性 T 细胞、嗜酸性粒细胞和调节性 T 细胞的积累,并降低 γδ(γδ)T 细胞中 IL-17A 的表达,从而改善修复并减少纤维化。rSEA 在水凝胶中的包封和控制释放进一步增强了 2 型免疫和更大体积的组织修复。rSEA 的广泛再生能力在关节和角膜损伤模型中得到了验证。这些结果介绍了一种使用天然寄生虫衍生物的再生免疫治疗方法。