Type 2 immunity induced by bladder extracellular matrix enhances corneal wound healing

膀胱细胞外基质诱导的 2 型免疫增强角膜伤口愈合

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作者:Xiaokun Wang, Liam Chung, Joshua Hooks, David R Maestas Jr, Andriana Lebid, James I Andorko, Luai Huleihel, Alexander F Chin, Matthew Wolf, Nathaniel T Remlinger, Mary Ann Stepp, Franck Housseau, Jennifer H Elisseeff

Abstract

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.

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