扁平苔藓（LP）损害组织中，Th1和细胞毒性T细胞（CTL）是主要的免疫效应细胞，但诱导其表型分化的机制不明。本团队在前一个国自然项目（81400512）中研究发现，浆细胞样树突状细胞（pDC）及其TLR9/IRF/IFN-α通路活化与口腔LP发病有关，而DC是唯一具有诱导初始T细胞分化的抗原提呈细胞。因此本项目假设：pDC的TLR9受体识别角质形成细胞（KC）来源的抗原，激活IRF/IFN-α通路，从而诱导初始T细胞向Th1-CTL方向分化，分化的效应性T细胞杀伤KC，最终形成LP损害。本研究以KC来源的HSP90-DNA复合物为TLR9激动剂，在体外制备HSP90hiKC-pDC-T细胞的Transwell共培养体系，在体内利用K14-HSP90转基因小鼠为受体+尾静脉移植pDCs的形式，验证上述通路在LP中诱导T细胞分化的作用，以阐明该通路在LP中的发病机制。

Th1 and cytotoxic T lymphocytes (CTL) are the major immune effective cells in lichen planus (LP), but the mechanism of their phenotype differentiation keeps unknown. In our previous grant (NSFC81400512), we found that the amount of plasmacytoid dendritic cells (pDCs) increased in LP. Further, their TLR9 receptor/IFN-α pathway activation was highly associated with the pathogenesis of LP. As dendritic cells are the only antigen presenting cells which could induce the differentiation of naive T cells, in the present study, we hypothesize that TLR9 of pDCs could recognize antigen derived from keratinocytes and lead to the activation of IRF/IFN-α signaling pathway so that the naive T cells would be induced to Th1 and CTLs. The induced T effectors would damage keratinocytes and, finally, LP lesion could be found. In-vitro and in-vivo experiments would be applied, to demonstrate whether the TLR9/IFN-α pathway of pDCs can induce a T cell immune phenotype differentiation and response against KC under skin and mucosa, thereby producing a pathological manifestation of KC death characterized in lichenoid lesions. (1)in vitro, KC-derived HSP90-DNA complex would be used as an agonist of TLR9/IFN-α pathway of pDC in a Transwell co-culture model; (2) Transgenic mice with high expression of HSP90 specifically in KC would be used as recipients, while HSP90-DNA pre-sensitized pDCs would be transplanted into the recipient mice to demonstrate the effect of TLR9/IFN-α pathway on the induction of KC death in vivo. In this way, we will evaluate the pathogenic role of the above pathways in LP and promoted the understanding of the immune pathogenesis of LP.