以新的T细胞亚群Th22为核心的免疫调控网络在口腔扁平苔藓发病中的作用

Oral lichen planus(OLP) is a T cell-mediated immune-related disease. The etiology and pathogenesis of OLP have not been well elucidated. The newly discovered T helper cell subset, Th22, has played an important role in the pathogenesis of several epithelial immune-related diseases. According to the results of previous studies of our group and recent advance in this research field, we made a hypothesis that Th22 cell and its related cytokines might have participated in the pathogenesisi of OLP through the activation of JAK/STAT、MAPK and other signal pathways. The following studies are designed to prove that hypothesis: ①Expression and distribution of Th22 cell and its related cytokines in the clinical samples of OLP; ②The role of Th22 cell and its effector cytokines on the proliferation, apoptosis, migration, differentiation and inflammation of oral keratinocytes and the possible signal pathways. The result of this research will shed a new light on the mechanism of interations between T lymphocytes and oral keratinocytes in the pathogenesis of OLP, thus facilitate the development of new therapeutic strategies to treat and prevent OLP and other chronic immune-related diseases.

目前公认，口腔扁平苔藓(OLP)是T细胞介导的慢性免疫相关性疾病，但其致病的T细胞亚群及其相应的作用网络未完全阐明。Th22是2009年才发现的新T细胞亚群，其与黏膜皮肤疾病的相关性受到关注，但未见其与OLP关系的报到。而本课题组前期研究提示：以Th22为核心的免疫调控网络可能通过激活JAK/STAT、MAPK等信号通路，调节OLP角质形成细胞的功能，参与OLP的发生和发展。为印证该假设，拟研究：①该免疫调控网络关键细胞和细胞因子在OLP临床样本中的表达分布规律；②该调控网络对OLP角质形成细胞增殖、凋亡、移行、分化以及炎症反应的调控作用；③该调控网络对OLP角质形成细胞的调控机制及相关的信号通路、关键调控因子。结果不仅有助于发现Th22与OLP的关系，更重要的是，利用OLP作为观测模型，进一步阐明Th22这一新细胞亚群与人类黏膜免疫与疾病的关系，并为寻找相关疾病的防治新靶点提供依据。

Th22细胞及其主要效应因子IL-22在免疫相关性疾病中发挥的作用近年来日益受到关注，但其在口腔扁平苔藓（OLP）发病中的作用和作用机制尚不明确。本课题研究发现：① 口腔角质形成细胞表达IL-22的特异性受体；OLP患者口腔黏膜局部，Th22细胞效应因子IL-22及其特异性受体IL-22R1的表达显著升高；IL-22和Th22细胞分化诱导因子IL-6、TNF-α在OLP患者外周血中的表达水平明显升高，且与OLP的临床亚型有关；②体外采用低浓度IL-22重组蛋白刺激口腔角质形成细胞，对细胞的增殖、凋亡、分化无显著影响，但可促进细胞的迁移和炎症因子的表达；③IL-22重组蛋白可激活JAK-STAT信号通路，选择性抑制该通路，可部分逆转IL-22对口腔角质形成细胞生物学行为的调控作用。综上，本研究得出以下结论：口腔角质形成细胞是Th22主要效应因子IL-22的靶细胞，IL-22作用于口腔角质形成细胞后，可能通过激活JAK-STAT通路影响口腔角质形成细胞的迁移炎症因子的表达，从而影响OLP的发生、发展。