促再生糖肽水凝胶通过巨噬细胞-T 细胞串扰激活 2 型免疫反应以促进伤口愈合,Advanced Functional Materials

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促再生糖肽水凝胶通过巨噬细胞-T 细胞串扰激活 2 型免疫反应以促进伤口愈合
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-01-02 , DOI: 10.1002/adfm.202307711
Jingrong Wang ₁ , Xiang Liu ₂ , Yaping Wang ₃ , Yushan Zhang ₁ , Rui Gao ₁ , Yu Gao ₁ , Pengxu Kong ₄ , Yini Huangfu ₂ , Chuangnian Zhang ₁ , Zujian Feng ₁ , Pingsheng Huang ₁ , Pengxiang Yang ₅ , Weiwei Wang ₁

Affiliation

免疫调节生物材料越来越多地应用于再生医学。人们发现仿生糖肽水凝胶可通过诱导巨噬细胞 M2 型极化来加速皮肤伤口愈合，然而，尚不清楚这是否可能协调促再生 T 细胞免疫。本研究的目的是通过甘露糖受体结合葡甘聚糖 (GM) 自组装的新型免疫调节糖肽水凝胶（称为 GRK^凝胶）增强巨噬细胞-T 细胞串扰，从而阐明组织再生中的修复性 T 细胞免疫反应化学嫁接有 RADA16 缀合的 T 细胞表位。糖肽可以被巨噬细胞吞噬和加工，然后巨噬细胞将肽呈递给幼稚 T 细胞，并通过 IL-4 依赖性 STAT6/GATA3 或 c-Maf 途径将其极化为 T 辅助细胞 2 (TH ₂ ) 细胞。引人注目的是，小鼠全层皮肤伤口修复表明，GRK^{凝胶通过激发 T}_H 2 免疫反应、增加 M2 巨噬细胞的驻留以及促进局部组织环境的血管生成，对恢复病理结构和毛囊具有卓越功效。。此外，基因组学结果说明了 GRK^凝胶作为免疫调节生态位、协调免疫细胞串扰和促进细胞外基质 (ECM) 重建的作用。总的来说，这项研究强调了免疫细胞之间的串扰在激发促愈合 T 细胞免疫方面的重要性，为内源性组织再生提供了一种有前景的无药物/细胞因子策略。

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Pro-Regenerative Glycopeptide Hydrogel Activates Type 2 Immune Response for Wound Healing via Macrophage-T Cell Crosstalk

Immunomodulatory biomaterials are increasingly used in regenerative medicine. Biomimetic glycopeptide hydrogel is found to accelerate cutaneous wound healing by inducing macrophage M2-type polarization, however, it is unclear whether this will possibly orchestrate a pro-regenerative T cell immunity. Here the aim of this study is to elucidate the reparative T-cell immune response in tissue regeneration by augmenting macrophage-T cell crosstalk with a novel immunomodulatory glycopeptide hydrogel (termed as GRK^gel) self-assembled by mannose receptor-binding glucomannan (GM) chemically grafted with RADA16-conjugated T-cell epitope. The glycopeptide can be phagocytized and processed by macrophages, which then presents peptides to naïve T cells and polarizes them into T helper 2 (T_H2) cells through IL-4-dependent STAT6/GATA3 or c-Maf pathways. Strikingly, full-thickness skin wound repair in mice indicates a superior efficacy of GRK^gel on restoring the pathological structure and hair follicle by provoking T_H2 immune response, increasing the residence of M2 macrophages, as well as promoting angiogenesis at the local tissue environment. Furthermore, genomics results illustrates the role of GRK^gel serving as an immunomodulatory niche, orchestrating immune cell crosstalk and promoting extracellular matrix (ECM) reconstruction. Collectively, this study highlights the significance of crosstalk between immune cells in evoking pro-healing T-cell immunity, providing a promising drug-/cytokine-free strategy for endogenous tissue regeneration.

更新日期：2024-01-02

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