Regulation and function of Id2 in plasmacytoid dendritic cells.
Regulation and function of Id2 in plasmacytoid dendritic cells.
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浆细胞样树突状细胞中 Id2 的调节和功能。
DOI：
10.1016/j.molimm.2022.05.009
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发表时间：
2022
影响因子：
3.6
通讯作者：
Watowich,StephanieS
中科院分区：
文献类型：
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作者：
Babcock,RachelL;Zhou,Yifan;Patel,Bhakti;Chrisikos,TaylorT;Kahn,LauraM;Dyevoich,AllisonM;Medik,YusraB;Watowich,StephanieS
浆细胞样树突状细胞（pDC）是特化的I型干扰素（IFN-I）产生细胞，其促进抗病毒免疫应答并有助于自身免疫。pDC的发育需要转录调节因子E2-2，并且受到DNA结合抑制剂2（Id 2）的抑制。先前的工作表明Id 2在pDC成熟后被诱导，并且可能通过抑制E2-2影响pDC IFN-I的产生，这表明Id 2在该谱系中具有重要但未表征的作用。我们发现TLR 7激动剂刺激pDC中Id 2 mRNA和蛋白的表达。我们进一步表明Id 2的转录激活依赖于E2泛素结合酶Ubc 13，但不依赖于响应TLR 7激动剂刺激的IFN-I信号。尽管如此，pDC中的条件性Id 2耗尽表明Id 2对于TLR 7激动剂诱导的成熟和E2-2表达的抑制是无效的。因此，我们确定了Ubc 13的Id 2调控的新机制，这可能与理解Id 2基因在其他情况下的调控有关，同时排除了Id 2在pDC对TLR 7激动剂的反应中的主要作用。
Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-I) producing cells that promote anti-viral immune responses and contribute to autoimmunity. Development of pDCs requires the transcriptional regulator E2–2 and is opposed by inhibitor of DNA binding 2 (Id2). Prior work indicatesId2is induced in pDCs upon maturation and may affect pDC IFN-I production via suppression of E2–2, suggesting an important yet uncharacterized role in this lineage. We found TLR7 agonists stimulate Id2 mRNA and protein expression in pDCs. We further show that transcriptional activation ofId2is dependent on the E2 ubiquitin-conjugating enzyme Ubc13, but independent of IFN-I signaling in response to TLR7 agonist stimulation. Nonetheless, conditionalId2depletion in pDCs indicates Id2 is dispensable for TLR7 agonist-induced maturation and inhibition of E2–2 expression. Thus, we identify new mechanisms of Id2 regulation by Ubc13, which may be relevant for understanding Id2 gene regulation in other contexts, while ruling out major roles for Id2 in pDC responses to TLR7 agonists.