窄谱中波紫外线（NB-UVB）主要通过促进黑素合成和抑制黑素细胞凋亡的双向作用治疗白癜风，但对不同患者存在疗效差异，其机制尚不清。本课题组前期：1）首次报道白癜风易感基因RNASET2；2）初步发现NB-UVB疗效差的患者皮肤组织中RNASET2高表达。我们提出假说：RNASET2高表达抑制NB-UVB诱导的黑素合成、促进黑素细胞凋亡，是导致NB-UVB疗效差的关键因素，RNASET2可成为改善NB-UVB疗效的作用靶点。本课题拟：1）扩大样本量进一步明确皮肤组织和外周血中RNASET2表达与NB-UVB疗效的相关性；2）通过RNASET2过表达和敲除/敲低的斑马鱼模型和细胞模型，探索RNASET2影响NB-UVB介导黑素合成和黑素细胞凋亡的调控机制；3）筛选抑制RNASET2表达，从而提高NB-UVB对白癜风疗效的潜在药物。本课题为NB-UVB疗效差异提供新机制和治疗新靶点。

Narrowband UVB (NB-UVB) could treat vitiligo through a dual effect on inhibiting melanin synthesis and promoting melanocyte apoptosis, while the therapeutic results vary among patients, and this mechanism is still unclear. In the earlier studies, we got following results: 1) for the first time, we reported that RNASET2 was a susceptibility gene for vitiligo; 2) the expression of RNASET2 was increased in skin tissue of patients with poor effect of NB-UVB therapy. We hypothesize that the high expression of RNASET2 could neutralize the dual effect of NB-UVB on the melanin synthesis and melanocyte apoptosis, which is the key factor to determine the curative effect of NB-UVB, and RNASET2 could be a new target to improve the therapeutic effect of NB-UVB. The current project aims: 1) to further confirm the relativity between the expression of RNASET2 in skin tissue and peripheral blood and therapeutic effect of NB-UVB with a bigger samples size; 2) to explore the regulating role of RNASET2 in NB-UVB mediated melanin biosynthesis and melanocyte apoptosis, through zebrafish and cell models with overexpression and knock-out/down of RNASET2; 3) to screen potential drugs that can inhibit RNASET2 expression and improve the treatment of vitiligo. The current project will provide new mechanism and target for the difference of curative effect with NB-UVB.