Cullin 3-Mediated Regulation of Intracellular Iron Homeostasis Promotes Thymic Invariant NKT Cell Maturation.
Cullin 3-Mediated Regulation of Intracellular Iron Homeostasis Promotes Thymic Invariant NKT Cell Maturation.
复制标题
DOI：
10.4049/immunohorizons.2300002
复制
发表时间：
2023-03-01
期刊：
影响因子：
--
通讯作者：
Chang CH
中科院分区：
文献类型：
--
作者：
Yarosz EL;Kumar A;Singer JD;Chang CH
E3泛素连接酶cullin 3(CUL3)对于不变NKT(INKT)细胞的发育至关重要，因为缺乏CUL3的iNKT细胞在未成熟的发育阶段积累。然而，CUL3介导iNKT细胞发育的机制尚不清楚。在这项研究中，我们利用T细胞特异性缺失CUL3的小鼠模型，研究了CUL3在未成熟和成熟胸腺iNKT细胞中的作用。我们发现，缺乏CUL3的成熟iNKT细胞比野生型细胞更容易增殖和死亡。这些细胞还表现出葡萄糖代谢增加和自噬。有趣的是，我们发现对铁稳态的严格调控对iNKT细胞的发育至关重要。在没有CUL3的情况下，成熟的iNKT细胞含有更高水平的胞质铁，这是一种与细胞死亡增加相关的表型。综上所述，我们的数据表明，CUL3促进iNKT细胞的发育部分是通过细胞内铁稳态。
The E3 ubiquitin ligase cullin 3 (Cul3) is critical for invariant NKT (iNKT) cell development, as iNKT cells lacking Cul3 accumulate in the immature developmental stages. However, the mechanisms by which Cul3 mediates iNKT cell development remain unknown. In this study, we investigated the role of Cul3 in both immature and mature thymic iNKT cells using a mouse model with a T cell–specific deletion of Cul3. We found that mature iNKT cells lacking Cul3 proliferated and died more than wild-type cells did. These cells also displayed increased glucose metabolism and autophagy. Interestingly, we found that tight regulation of iron homeostasis is critical for iNKT cell development. Without Cul3, mature iNKT cells harbored higher levels of cytosolic iron, a phenotype associated with increased cell death. Taken together, our data suggest that Cul3 promotes iNKT cell development partially through intracellular iron homeostasis.