Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice
Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice
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DOI：
10.1126/sciadv.abd1866
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发表时间：
2021-03-01
期刊：
影响因子：
13.6
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
--
作者：
Dai, Zhenpeng;Wang, Eddy Hsi Chun;Christiano, Angela M.
白细胞介素-7 （interleukin-7, IL-7）信号通路在T细胞功能和存活调控中起重要作用。我们在患有斑秃（一种T细胞介导的毛囊自身免疫性疾病）的人和C3H/HeJ小鼠的皮损皮肤中检测到IL-7的过表达。我们发现外源性IL-7通过增加脱发T细胞的扩增来加速AA的发生。相反，阻断IL-7可阻止C3H/HeJ小鼠AA的进展并逆转早期AA。在机制上，我们观察到IL-7R α阻断大大减少了大多数T细胞亚群的总数，但相对保留了调节性T细胞（T-regs）。我们假设短期抗il - 7r α治疗联合低剂量的促t细胞因子可能改善AA的治疗效果。我们证明短期IL-7R α阻断联合低剂量促t细胞因子可增强治疗AA的疗效，并有待进一步的临床研究。
The interleukin-7 (IL-7) signaling pathway plays an important role in regulation of T cell function and survival. We detected overexpression of IL-7 in lesional skin from both humans and C3H/HeJ mice with alopecia areata (AA), a T cell-mediated autoimmune disease of the hair follicle. We found that exogenous IL-7 accelerated the onset of AA by augmenting the expansion of alopecic T cells. Conversely, blockade of IL-7 stopped the progression of AA and reversed early AA in C3H/HeJ mice. Mechanistically, we observed that IL-7R alpha blockade substantially reduced the total number of most T cell subsets, but relative sparing of regulatory T cells (T-regs). We postulated that short-term anti-IL-7R alpha treatment in combination with a low dose of T-reg-tropic cytokines might improve therapeutic efficacy in AA. We demonstrated that short-term IL-7R alpha blockade in combination with low doses of T-reg-tropic cytokines enhanced therapeutic effects in the treatment of AA, and invite further clinical investigation.