Loss-of-function mutations in SKIV2L underlie trichohepatoenteric syndrome (THES2), a rare inborn error of immunity characterized by diarrhea, skin lesions, brittle hair, and immunodeficiency. SKIV2L is part of a multiprotein complex required for exosome-mediated RNA surveillance through RNA decay. In this issue of the JCI, Yang et al. delineate a mechanism underlying autoinflammatory skin disease in Skiv2l-deficient mice. Thus, a lack of SKIV2L activates mTORC1 signaling in keratinocytes and T cells, impeding skin barrier integrity and T cell homeostasis. Interestingly, treatment with the mTOR inhibitor rapamycin improves skin symptoms in Skiv2l-deficient mice, suggesting a possible therapeutic avenue for patients with THES2.

中文翻译：

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mTORC1对RNA压力的感知驱动自身炎症

SKIV2L的功能丧失突变是毛肝肠综合征 (THES2) 的基础，这是一种罕见的先天性免疫缺陷，其特征是腹泻、皮肤损伤、脆弱的头发和免疫缺陷。SKIV2L 是通过 RNA 衰变进行外泌体介导的 RNA 监测所需的多蛋白复合物的一部分。在本期JCI中，Yang 等人。描述Skiv2l 缺陷小鼠自身炎症性皮肤病的潜在机制。因此，缺乏 SKIV2L 会激活角质形成细胞和 T 细胞中的 mTORC1 信号传导，从而阻碍皮肤屏障完整性和 T 细胞稳态。有趣的是，用 mTOR 抑制剂雷帕霉素治疗可以改善Skiv2l 缺陷小鼠的皮肤症状，这表明可能为 THES2 患者提供治疗途径。