CCL17-CCR4 轴促进小鼠白癜风的发病。
CCL17-CCR4 axis contributes to the onset of vitiligo in mice.
机构信息
Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Department of Pharmacy, Eye Ear Nose & Throat Hospital, Fudan University, Shanghai, China.
出版信息
Immun Inflamm Dis. 2021 Sep;9(3):702-709. doi: 10.1002/iid3.423. Epub 2021 Jun 2.
BACKGROUND
Destruction of melanocytes mediated by autoimmunity is currently believed as the main cause of vitiligo. This article aims to identify the role of CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) axis in vitiligo and provide new possibilities for the clinical treatment of vitiligo.
METHODS
A total of 30 patients with vitiligo from Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University were recruited based on the inclusion and exclusion criteria. Trephine was used to obtain skin samples from the lesion area and its surrounding normal areas, and the expression levels of CCL17, CCR4, Tbx21, Eomes, and Blimp1 were determined by quantitative reverse transcription polymerase chain reaction. Vitiligo mouse model was established by adoptively transferring CFP-PMEL CD8+ T cells into sublethally irradiated Krt14-Kitl* mice. Recipient mice received intraperitoneal injection of 1 × 10 plaque-forming units of rVV-hPMEL on the same day of transfer. The degree of depigmentation was scored blindly by one observer 5 weeks after vitiligo induction. CFP-PMEL CD8+ T cells migration to skin, draining lymph nodes, spleen, and blood were detected by flow cytometry. CCR4 blockade was performed by intraperitoneal injection of neutralizing antibody.
RESULTS
The expression levels of CCL17, CCR4, Tbx21, Eomes, and Blimp1 in skin lesions were significantly increased compared with that in surrounding normal areas. CCL17 and CCR4 mice exhibited significantly lower disease scores than WT mice. The CFP-PMEL CD8+ T cells accumulation was significantly decreased in the skin of CCL17 and CCR4 mice, but was not changed in draining lymph nodes, spleen, and blood. Administration of CCR4 neutralizing antibody decreased the degree of depigmentation and the recruitment of CFP-PMEL CD8+ T cells to the skin, while keeping the number of T cells in draining lymph nodes unchanged.
CONCLUSION
Targeting CCL17-CCR4 axis might inhibit T cell migrating to skin and alleviate vitiligo progression.
背景
目前认为黑色素细胞的自身免疫破坏是白癜风的主要原因。本文旨在探讨趋化因子配体 17（CCL17）-趋化因子受体 4（CCR4）轴在白癜风中的作用，为白癜风的临床治疗提供新的可能性。
方法
根据纳入和排除标准，共招募了 30 名南京医科大学附属淮安第一人民医院的白癜风患者。使用环钻从病变区域及其周围正常区域获取皮肤样本，通过定量逆转录聚合酶链反应测定 CCL17、CCR4、Tbx21、Eomes 和 Blimp1 的表达水平。通过将 CFP-PMEL CD8+T 细胞过继转移到亚致死照射的 Krt14-Kitl*小鼠中建立白癜风小鼠模型。在转移的同一天，受体小鼠接受 1×10 个空斑形成单位的 rVV-hPMEL 腹腔内注射。白癜风诱导后 5 周，由一名观察者对脱色素程度进行盲法评分。通过流式细胞术检测 CFP-PMEL CD8+T 细胞向皮肤、引流淋巴结、脾脏和血液中的迁移。通过腹腔内注射中和抗体进行 CCR4 阻断。
结果
与周围正常区域相比，皮损处 CCL17、CCR4、Tbx21、Eomes 和 Blimp1 的表达水平明显升高。CCL17 和 CCR4 小鼠的疾病评分明显低于 WT 小鼠。CCL17 和 CCR4 小鼠皮肤中 CFP-PMEL CD8+T 细胞的聚集明显减少，但引流淋巴结、脾脏和血液中的细胞数量没有变化。CCR4 中和抗体的给药降低了脱色素程度和 CFP-PMEL CD8+T 细胞向皮肤的募集，同时保持引流淋巴结中 T 细胞的数量不变。
结论
靶向 CCL17-CCR4 轴可能抑制 T 细胞迁移到皮肤并缓解白癜风的进展。
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