除了抑制免疫反应外，调节性 T 细胞 (Treg) 还能维持组织稳态并控制全身代谢。铁是否参与 Treg 介导的耐受性尚不清楚。在这里，我们发现转铁蛋白受体 CD71 在浸润人类肝癌的激活的 Tregs 上表达上调。患有 Treg 限制性 CD71 缺陷的小鼠会自发地出现一种类似皮癣的疾病，这是由围产期 Treg 扩张受损引起的。 CD71 缺失的 Treg 表现出增殖减少和组织 Treg 特征丢失。在围产期，Tregs 中的 CD71 缺乏会引发肝脏铁超负荷反应，其特征是铁调素转录增加和巨噬细胞中铁积累。在 CD71 条件性敲除新生儿的粪便微生物群中检测到细菌多样性较低，有益物种减少。我们的研究结果表明，CD71 介导的铁吸收是 Treg 围产期扩张所必需的，并且与全身铁稳态和细菌肠道定植有关。因此，我们假设 Tregs 在出生后细菌定植期间通过竞争铁来建立营养耐受性。

Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth.