Mitf is required for T cell maturation by regulating dendritic cell homing to the thymus
Mitf is required for T cell maturation by regulating dendritic cell homing to the thymus
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Mitf 通过调节树突状细胞归巢至胸腺来实现 T 细胞成熟
DOI：
10.1016/j.bbrc.2022.01.091
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Nishimura EK,?Takubo K.
中科院分区：
文献类型：
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作者：
Karigane D;Haraguchi M;Toyama-Sorimachi N;Nishimura EK,?Takubo K.
胸腺树突状细胞（dc）通过调节胸腺自身反应性T细胞的负选择来促进免疫耐受。DC归巢到胸腺是如何被转录调控的尚不清楚。小眼相关转录因子（Mitf）广泛表达，在造血系统中起重要作用。在这里，我们使用mitf突变小鼠（Mitfvit/vit），发现胸腺肿大，CD4/CD8双阳性T细胞增多。mitf在造血系统中胸腺dc的一个亚群中高度表达。基因突变或药物抑制dc中的Mitf降低了itga4的表达水平，而itga4是dc归巢到胸腺的关键分子。此外，抑制Mitf降低胸腺DC数。这些结果表明，通过调节DC亚群在胸腺内的归巢，mitt在维持T细胞分化中起着关键作用。
Thymic dendritic cells (DCs) promote immune tolerance by regulating negative selection of autoreactive T cells in the thymus. How DC homing to the thymus is transcriptionally regulated is still unclear. Microphthalmia-associated transcription factor (Mitf) is broadly expressed and plays essential roles in the hematopoietic system. Here, we usedMitf-mutated mice (Mitfvit/vit) and found enlargement of the thymus and expansion of CD4/CD8 double-positive T cells.Mitfwas highly expressed in a subset of thymic DCs among the hematopoietic system. Genetic mutation or pharmacological inhibition of Mitf in DCs decreased the expression levels ofItga4, which are critical molecules for the homing of DCs to the thymus. Further, inhibition of Mitf decreased thymic DC number. These results suggest a pivotal role ofMitfin the maintenance of T cell differentiation by regulating the homing of DC subsets within the thymus.