T cell‐expressed microRNAs critically regulate germinal center T follicular helper cell function and maintenance in acute viral infection in mice,European Journal of Immunology

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T cell‐expressed microRNAs critically regulate germinal center T follicular helper cell function and maintenance in acute viral infection in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-09-30 , DOI: 10.1002/eji.202048867
Julia Zeiträg ₁ , Frank Dahlström ₁ , Yinshui Chang ₁ , Dominik Alterauge ₁ , Daniel Richter ₂ , Julia Niemietz ₁ , Dirk Baumjohann _{1,

3}

Affiliation

Constitutive T cell‐intrinsic miRNA expression is required for the differentiation of naïve CD4⁺ T cells into Tfh cells, thus making it difficult to study the role of miRNAs in the maintenance of already established Tfh cells and ongoing germinal center (GC) responses. To overcome this problem, we here used temporally controlled ablation of mature miRNAs specifically in CD4⁺ T cells during acute LCMV infection in mice. T cell‐intrinsic miRNA expression was not only critical at early stages of Tfh cell differentiation, but also important for the maintenance of already established Tfh cells. In addition, CD4⁺ T cell‐specific ablation of miRNAs resulted in impaired GC B cell responses. Notably, miRNA deficiency also compromised the antigen‐specific CD4⁺ T cell compartment, Th1 cells, Treg cells, and Tfr cells. In conclusion, our results highlight miRNAs as important regulators of Tfh cells, thus providing novel insights into the molecular events that govern T cell–B cell interactions and Th cell identity.

中文翻译：

T细胞表达的microRNA关键调节小鼠急性病毒感染中生发中心T滤泡辅助细胞的功能和维持

要使幼稚的CD4 ⁺ T细胞分化为Tfh细胞，就需要本构性的T细胞内在性miRNA表达，因此难以研究miRNA在维持已建立的Tfh细胞和持续的生发中心（GC）反应中的作用。为了克服这个问题，我们在小鼠急性LCMV感染期间在CD4 ⁺ T细胞中特异性地使用了成熟的miRNA的时间控制消融。T细胞固有的miRNA表达不仅在Tfh细胞分化的早期至关重要，而且对于维持已经建立的Tfh细胞也很重要。另外，miRNA的CD4 ⁺ T细胞特异性消融导致GC B细胞反应受损。值得注意的是，miRNA缺乏也损害了抗原特异性CD4⁺ T细胞区室，Th1细胞，Treg细胞和Tfr细胞。总之，我们的结果强调了miRNA是Tfh细胞的重要调节剂，从而为控制T细胞-B细胞相互作用和Th细胞身份的分子事件提供了新颖的见解。

更新日期：2020-09-30

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