T cell-expressed microRNAs critically regulate germinal center T follicular helper cell function and maintenance in acute viral infection in mice

Constitutive T cell-intrinsic miRNA expression is required for the differentiation of naive 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.

Automated summary

The expression of constitutive T cell-intrinsic miRNAs is crucial for the differentiation and maintenance of Tfh cells, as well as for the GC B cell responses. Deficiency of miRNAs in CD4(+) T cells not only impairs the GC B cell responses, but also affects antigen-specific CD4(+) T cell subsets, Th1 cells, Treg cells, and Tfr cells. Overall, miRNAs play a significant role in regulating Tfh cells and T cell-B cell interactions.