Regulation of Hematopoietic Inflammatory Signaling by MIRC11 and miR-146a

Although chronic inflammation impairs normal hematopoiesis, a low level of inflammatory signaling is essential for maintaining hematopoietic stem cell (HSC) homeostasis. Here, we report that mice lacking MiRNA Cluster 11 (Mirc11: encodes miR-23a, miR-24-2, and miR-27a) display reduced inflammatory signaling, including diminished IFN-α/β, IFN-γ, TNF, IL-6, and Toll-like receptor (TLR) pathway activity.

Notably, this phenotype is opposite of that seen in miR146a-deficient mice, which exhibit hyperinflammation leading to bone marrow failure. These contrasting phenotypes suggest that Mirc11 miRNAs and miR-146a may function together to buffer inflammatory signaling and maintain immune homeostasis.