Exosomal PD-L1 functions as an immunosuppressant to promote wound healing.
Exosomal PD-L1 functions as an immunosuppressant to promote wound healing.
复制标题
外泌体 PD-L1 作为免疫抑制剂促进伤口愈合
DOI：
10.1080/20013078.2019.1709262
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发表时间：
2019-12-27
影响因子：
16
通讯作者：
Cheng F
中科院分区：
文献类型：
--
作者：
Su D;Tsai HI;Xu Z;Yan F;Wu Y;Xiao Y;Liu X;Wu Y;Parvanian S;Zhu W;Eriksson JE;Wang D;Zhu H;Chen H;Cheng F
损伤后过度和持续的炎症会导致慢性伤口，增加组织损伤甚至侵袭性致癌转化。有效的伤口修复可以通过抑制过度活跃的免疫细胞到达损伤部位来实现。在这项研究中，我们从过表达PD-L1的基因工程细胞或IFN-γ刺激的细胞中获得了外泌体中高浓度的PD-L1。我们发现外泌体PD-L1与T细胞表面的PD-1特异性结合，并抑制T细胞活化。有趣的是，当与T细胞预孵育时，外泌体PD-L1促进表皮细胞和真皮成纤维细胞的迁移。我们进一步将外泌体包埋到温度响应性PF-127水凝胶中，该水凝胶在体温下胶化以持续的方式将外泌体释放到周围环境中。重要的是，在小鼠皮肤切除伤口模型中，当在炎症阶段包埋在水凝胶中时，外泌体PD-L1显著加快伤口收缩和上皮再生。最后，外泌体PD-L1抑制CD 8 + T细胞的细胞因子产生，并抑制脾脏和外周淋巴结中的CD 8 + T细胞数量。总之，这些数据提供了外泌体PD-L1发挥免疫抑制作用和促进组织修复的证据。
ABSTRACT Excessive and persistent inflammation after injury lead to chronic wounds, increased tissue damage or even aggressive carcinogenic transformation. Effective wound repair could be achieved by inhibiting overactive immune cells to the injured site. In this study, we obtained high concentration of PD-L1 in exosomes from either genetically engineered cells overexpressing PD-L1 or IFN-γ stimulated cells. We found that exosomal PD-L1 is specially bound to PD-1 on T cell surface, and suppressed T cell activation. Interestingly, exosomal PD-L1 promoted the migration of epidermal cells and dermal fibroblasts when pre-incubated with T cells. We further embedded exosomes into thermoresponsive PF-127 hydrogel, which was gelatinized at body temperature to release exosomes to the surroundings in a sustained manner. Of importance, in a mouse skin excisional wound model, exosomal PD-L1 significantly fastened wound contraction and reepithelialization when embedded in hydrogel during inflammation phase. Finally, exosomal PD-L1 inhibited cytokine production of CD8+ T cells and suppressed CD8+ T cell numbers in spleen and peripheral lymph nodes. Taken together, these data provide evidence on exosomal PD-L1 exerting immune inhibitory effects and promoting tissue repair.
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影响因子：
64.8
作者：
Karin M;Clevers H
通讯作者：
Clevers H
DOI：
10.1111/bjd.13954
发表时间：
2015-08
期刊：
The British journal of dermatology
影响因子：
--
作者：
Martin P;Nunan R
通讯作者：
Nunan R
影响因子：
17.1
作者：
Eming SA;Martin P;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
4.6
作者：
Muller L;Mitsuhashi M;Simms P;Gooding WE;Whiteside TL
通讯作者：
Whiteside TL