瘢痕疙瘩被称为良性真皮肿瘤，持续增殖并向周边正常皮肤侵袭生长。免疫调节剂—糖皮质激素是瘢痕疙瘩的一线治疗药物，临床治疗中仍存在较高复发率。项目组前期发现诸多信号转导通路参与瘢痕疙瘩形成。进一步分析瘢痕疙瘩与正常皮肤在激素治疗前后的基因表达谱芯片数据，发现30个特异性显著改变的差异基因。其中，淋巴细胞抗原6-复合体K（LY6K）这一T细胞免疫相关基因在瘢痕疙瘩中表达显著降低，经激素治疗后表达显著升高。并且LY6K在瘢痕疙瘩中并非表达于抗原递呈细胞，而是特异地表达在表皮基底部的角质形成细胞。本项目拟通过瘢痕疙瘩角质形成细胞、T细胞、成纤维细胞原代分离及共培养、构建骨髓移植嵌合体裸鼠模型开展体内外实验，研究LY6K相关T细胞免疫对瘢痕疙瘩内角质形成细胞-淋巴细胞-成纤维细胞网络的调控效应，深入探讨瘢痕疙瘩纤维化发生发展中免疫信号通路的调控机制，寻找瘢痕疙瘩特异性治疗靶点，以改善疾病预后。

Keloid is known as benign dermal tumor, characterized with persistent proliferation and invasive growth to the surrounding normal skin. Immunomodulator - glucocorticoid is the first-line treatment of keloid. However, there is still a high rate of recurrence in clinical treatment. Our team have found a lot of signal transduction pathways involved in the formation of keloid. Further analysis of gene expression profile from chip data of keloid and normal skin tissue before and after treatment of glucocorticoid found 30 specific changed genes with significant differences. The results suggest that expression level of LY6K, a T cell immunity-related gene, was significantly reduced in keloid compared with normal skin, while increased after treatment of glucocorticoid. Furthermore, we found that LY6K was not expressed in antigen presenting cells such as macrophages in keloid, but specifically expressed in keratinocytes of the epidermal base. This study is designed to investigate the effect and mechanism of LY6K-related T cell immunity on keratinocyte- lymphocyte -fibroblast network in keloid through in vivo and in vitro experiments using co-culture of primary isolated keratinocyte, lymphocyte and fibroblast, together with a bone marrow transplantation chimeric nude mice keloid model. The mechanism of immunological signaling pathway in the development of keloid fibrosis will be explored in depth to find specific treatment target for keloid, in order to improve the prognosis for the patient.