FOXP3 gene is a key transcription factor driving immune tolerance and its deficiency causes immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (IPEX), a prototypic primary immune regulatory disorder (PIRD) with defective regulatory T (Treg) cells. Although life-threatening, the increased awareness and early diagnosis have contributed to improved control of the disease. IPEX currently comprises a broad spectrum of clinical autoimmune manifestations from severe early onset organ involvement to moderate, recurrent manifestations. This review focuses on the mechanistic advancements that, since the IPEX discovery in early 2000, have informed the role of the human FOXP3+ Treg cells in controlling peripheral tolerance and shaping the overall immune landscape of IPEX patients and carrier mothers, contributing to defining new treatments.

中文翻译：

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FOXP3缺陷，从疾病机制到治疗策略

FOXP3 基因是驱动免疫耐受的关键转录因子，其缺陷会导致免疫失调、多内分泌病、肠病 X 连锁综合征 (IPEX)、一种具有缺陷的调节性 T (Treg) 细胞的原型原发性免疫调节障碍 (PIRD)。尽管危及生命，但认识的提高和早期诊断有助于改善对该疾病的控制。IPEX 目前包括广泛的临床自身免疫表现，从严重的早发性器官受累到中度的复发性表现。本综述重点关注自 2000 年初发现 IPEX 以来的机制进展，这些进展揭示了人类 FOXP3+ Treg 细胞在控制外周耐受性和塑造 IPEX 患者和携带者母亲的整体免疫环境方面的作用，有助于确定新的治疗方法。