CCR5 is a novel target for the treatment of experimental alopecia areata.
CCR5 is a novel target for the treatment of experimental alopecia areata.
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CCR5是治疗实验性斑秃的新靶点。
DOI：
10.1002/cia2.12092
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Tokura Y.
中科院分区：
文献类型：
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作者：
Ito T;Suzuki T;Funakoshi A;Fujiyama T;Tokura Y.
斑秃（Alopecia areata，AA）是一种器官特异性、细胞介导的自身免疫性疾病。毛囊自身抗原公开给这些自身反应性NKG 2D + CD 8 +T细胞。一种Th 1趋化因子CXCL 10在毛囊角质形成细胞上高度表达，并导致CXCR 3+和CCR 5 + Th 1或Tc 1细胞在AA病变中的生长期毛囊周围浸润。AimTo评估CCR 5作为治疗实验性AA的新候选靶点。IL-15和CD 3/CD 25 Dynabeads，来自患有自发性AA的C3 H/HeJ小鼠。然后，330 μg/d的马拉韦罗，一个负变构调节剂的CCR 5受体，已经用于治疗患者与人类免疫缺陷病毒，口服给药28 days.ResultsWe成功地治疗了实验AA病变的C3 H/HeJ小鼠马拉韦罗。此外，CCR 5阻断可防止活化T细胞转移的C3 H/HeJ小鼠中AA的发展。有趣的是，用马拉韦罗治疗的实验性AA的C3 H/HeJ小鼠在2周后显示出脱发病变的改善。免疫组织学评估和FACS分析显示，马拉韦罗治疗后，病变中的CD 4 + CCR 5+和CD 8 + CCR 5 +T细胞数量减少。一项真实的实时水平趋化性试验显示，maraviroc可显著抑制CD 8 +LN细胞对RANTES的趋化活性。此外，与磷酸盐缓冲液相比，CCR 5阻断剂可阻止实验性AA的发展。结论CCR 5似乎是治疗AA的一个有希望的新候选靶点。CCR 5阻断可防止AA的发展以及改善AA病变。
BackgroundAlopecia areata (AA) is an organ‐specific and cell‐mediated autoimmune disease. Hair follicle autoantigens are disclosed to these autoreactive NKG2D+CD8+T cells. A Th1 chemokine, CXCL10, is highly expressed on hair follicle keratinocytes and leads to the infiltration of CXCR3+and CCR5+Th1 or Tc1 cells around anagen hair follicles in AA lesions.AimTo evaluate CCR5 as a new candidate target for the treatment of experimental AA.MethodsWe initiated 7‐month‐old female C3H/HeJ mice with intracutaneous injections of lymph node (LN) cells, which were activated by IL‐2, IL‐7, IL‐15, and CD3/CD25 Dynabeads, from C3H/HeJ mice with spontaneous AA. Then, 330 μg/d of maraviroc, a negative allosteric modulator of the CCR5 receptor that is already used for treating patients with human immunodeficiency virus, was orally administrated for 28 days.ResultsWe successfully treated the experimental AA lesions of C3H/HeJ mice with maraviroc. In addition, CCR5 blockade prevented the development of AA in activated T cell‐transferred C3H/HeJ mice. Interestingly, maraviroc‐treated C3H/HeJ mice with experimental AA showed improvement of hair loss lesions after 2 weeks. Immunohistological assessments and FACS analysis revealed a decreased number of CD4+CCR5+and CD8+CCR5+T cells in the lesions after maraviroc treatment. A real‐time horizontal chemotaxis assay showed that maraviroc significantly inhibited the chemotactic activity of CD8+LN cells toward RANTES. Furthermore, CCR5 blockade prevented experimental AA development when compared to phosphate‐buffered saline.ConclusionCCR5 appears to be a promising new candidate target for the treatment of AA. CCR5 blockade may prevent the development of AA as well as improve AA lesions.