组织常驻记忆性T细胞通过IL-15-颗粒酶B/穿孔素损伤黑素细胞机制研究

自身免疫在白癜风发病中起着重要作用，2016年我们课题组研究发现：CD8+CXCR3+T细胞在白癜风患者外周血中比例升高，特别是进展期白癜风患者。治疗后，白癜风患者外周血和皮损中CXCR3表达下降，提示白癜风患者体内存在过度活化的CXCL10/CXCR3轴，活化和趋化T细胞至白癜风皮损处，但是具体哪一群T细胞亚群尚不明了。最新文献报道，CD8+组织常驻型记忆性T细胞表达CXCR3，可能参与白癜风自身免疫机制，结合我们预实验结果：白癜风皮损处组织常驻型记忆性T细胞相比正常皮肤比例升高，由此推断：CXCR3+CD8+组织常驻型记忆性T细胞启动免疫记忆，通过IL-15-颗粒酶B/穿孔素途径，诱导免疫应答，促使黑素细胞受到免疫攻击而破坏，从而引起黑素细胞凋亡，参与白癜风的发病或复发。因此，拟通过白癜风患者和白癜风小鼠模型在体探讨组织常驻型记忆性T细胞介导损伤黑素细胞的分子机制。

Autoimmunity plays an important role in the pathogenesis of vitiligo. In 2016, our study showed that CXCR3+CD8+ T cells increased in peripheral blood of patients with vitiligo, especially in progressive vitiligo patients. By comparing the expression of CXCR3 in peripheral blood and lesion in vitiligo patients before and after treatment, we found an excessive activation of CXCL10/CXCR3 axis, however, which kind of specific subpopulation of T cells was still unknown. The latest research showed that resident memory T cells expressed CXCR3 which involved in the autoimmune mechanism of vitiligo. Our pilot study found that resident memory T cells increased in vitiligo lesion compared with normal skin. Thus, the hypothesis could be that CXCR3+CD8+ resident memory T cells in vitiligo lesion attack melanocytes by IL-15/ granzyme B/perforin pathway resulting melanocytes apoptosis. Therefore, we will investigate molecular mechanism of resident memory T cell role on melanocytes destruction or vitiligo reoccur.