Prolonged skin grafts survival time by IFN-gamma in allogeneic skin transplantation model during acute rejection through IFN-gamma/STAT3/IDO pathway in epidermal layer
Prolonged skin grafts survival time by IFN-gamma in allogeneic skin transplantation model during acute rejection through IFN-gamma/STAT3/IDO pathway in epidermal layer
复制标题
通过表皮层 IFN-gamma/STAT3/IDO 途径，在同种异体皮肤移植模型中，在急性排斥反应期间，IFN-gamma 延长了皮肤移植物的存活时间
DOI：
10.1016/j.bbrc.2017.12.152
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发表时间：
2018
影响因子：
3.1
通讯作者：
Hu Dahai
中科院分区：
文献类型：
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作者：
Zhang Yijie;Wang Yunchuan;Wu Gaofeng;Zhang Wei;Wang Xujie;Cai Weixia;Zhang Julei;Han Shichao;Li Yan;Bai Xiaozhi;Shi Jihong;Su Linlin;Hu Dahai
同种异体皮肤移植是多种疾病的救命疗法，包括大面积烧伤、大面积创伤和某些术后并发症。然而，急性排斥反应阻碍了同种异体皮肤移植的临床应用。尽管已经开发出许多新的免疫抑制药物，但仍需要一种并发症少、疗效好的理想治疗方法。在这里，我们发现干扰素γ (IFN-γ)作为一种免疫调节细胞因子可以延长同种异体移植物的存活时间，从（8.50 ± 1.517）天延长到（14.83 ± 2.714）天。吲哚胺- 2,3 -双加氧酶（IDO）被认为在诱导免疫耐受中起关键作用。通过体外组织培养、原代角质形成细胞和成纤维细胞，我们研究了IFN-γ对IDO表达的调节作用。IFN-γ通过STAT3磷酸化上调IDO表达，这种上调通过STAT3磷酸化抑制剂消除STAT3磷酸化而降低。有趣的是，IFN-γ诱导的IDO表达主要在表皮而非真皮层。与这些结果一致，IFN-γ在角质形成细胞中显著触发IDO表达，而不是成纤维细胞。综上所述，这表明IFN-γ可能是急性排斥反应的潜在免疫调节药物，表皮角质形成细胞可能在异体皮肤移植后的免疫耐受中起主要作用。
Allogeneic skin transplantation is the life-saving therapy for multiple diseases, including extensive burn, large-scale trauma and certain post-surgical complications. However, acute rejection impedes clinical application of allogeneic skin transplantation. Although a lot of novel immunosuppressant drugs have been developed, there is still great need for ideal therapy with less complication and more therapeutic effects. Here, we found interferon gamma (IFN-γ) as an immunomodulatory cytokine prolonged the survival time of allografts from (8.50 ± 1.517) days to (14.83 ± 2.714) days at best. Indoleamine-2, 3-dioxygenase (IDO) has been proposed to play key roles in induction of immune tolerance. Usingin vitrotissue culture and primary keratinocytes and fibroblasts, we investigated the regulatory effects of IFN-γ on the IDO expression. IFN-γ upregulated IDO expression through STAT3 phosphorylation and this upregulation was reduced by abolition of STAT3 phosphorylation through a STAT3 phosphorylation inhibitor. Interestingly, IFN-γ induced IDO expression predominately in epidermis rather than dermis. In consistent with these results, IFN-γ significantly triggered IDO expression in keratinocytes but not fibroblasts. Taken together, this suggests that IFN-γ might be a potential immunomodulatory drug in acute rejection and keratinocytes in epidermis may play a main role in immune tolerance after allogeneic skin transplantation.