Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sci Adv. 2021 Apr 16;7(16). doi: 10.1126/sciadv.abe2635. Print 2021 Apr.
The avascular nature of cornea tissue limits its regenerative potential, which may lead to incomplete healing and formation of scars when damaged. Here, we applied micro- and ultrafine porcine urinary bladder matrix (UBM) particulate to promote type 2 immune responses in cornea wounds. Results demonstrated that UBM particulate substantially reduced corneal haze formation as compared to the saline-treated group. Flow cytometry and gene expression analysis showed that UBM particulate suppressed the differentiation of corneal stromal cells into α-smooth muscle actin-positive (αSMA) myofibroblasts. UBM treatments up-regulated interleukin-4 (IL-4) produced primarily by eosinophils in the wounded corneas and CD4 T cells in draining lymph nodes, suggesting a cross-talk between local and peripheral immunity. Gata1 mice lacking eosinophils did not respond to UBM treatment and had impaired wound healing. In summary, stimulating type 2 immune responses in the wounded cornea can promote proregenerative environments that lead to improved wound healing for vision restoration.
角膜组织的无血管特性限制了其再生潜力,因此当受损时可能导致愈合不完全和形成疤痕。在这里,我们应用微和超细猪尿囊膜(UBM)颗粒来促进角膜伤口中的 2 型免疫反应。结果表明,与生理盐水处理组相比,UBM 颗粒显著减少了角膜混浊的形成。流式细胞术和基因表达分析表明,UBM 颗粒抑制了角膜基质细胞分化为 α-平滑肌肌动蛋白阳性(αSMA)成肌纤维细胞。UBM 处理上调了白细胞介素 4(IL-4)的产生,主要由伤口角膜中的嗜酸性粒细胞和引流淋巴结中的 CD4 T 细胞产生,表明局部和外周免疫之间存在串扰。缺乏嗜酸性粒细胞的 Gata1 小鼠对 UBM 治疗没有反应,并且伤口愈合受损。总之,刺激受伤角膜中的 2 型免疫反应可以促进有利于再生的环境,从而改善伤口愈合以恢复视力。