IRF7 suppresses hematopoietic regeneration under stress via CXCR4

Abstract

Hematopoietic stem cells (HSCs) maintain quiescence under steady state; however, they are compelled to proliferate and expand to replenish the blood system under stress. The molecular basis underlying stress hematopoiesis remains to be fully understood. In this study, we reported that IRF7 represents an important regulator of stress hematopoiesis. Interferon regulatory factor 7 (IRF7) was dispensable for normal hematopoiesis, whereas its deficiency significantly enhanced hematopoietic stem and progenitor cells (HSPCs) regeneration and improved long-term repopulation of HSCs under stress. Mechanistic studies showed that CXCR4 was identified as a downstream target of IRF7. Overexpression of CXCR4 abrogated the enhanced proliferation and regeneration of IRF7-deficient HSPCs under stress. Similar results were obtained in HSCs from human umbilical cord blood. These observations demonstrated that IRF7 plays an important role in hematopoietic regeneration under stress.

Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells

“…Additionally, IPA analysis revealed that the dual drug treatment led to a significant decrease in the expression of genes involved in inflammation ( Figure 3 B). Consistent with these findings, Irf7 (interferon regulatory factor 7), 32 a key transcriptional regulator of type I interferon (IFN)-dependent immune response, was significantly repressed in mutant cells treated with a combination of the two drugs ( Figure 3 C). Consistent with the observations made utilizing IPA, GSEA also revealed that GOF Shp2 E76K/+ mice treated with the dual drug combination resulted in decreased PI3Kinase signaling (NES: −1.99, p < 0.001), inositol phosphate metabolism (NES: −1.92, p < 0.001), BCR signaling pathway (NES: −1.67, p < 0.001), extracellular matrix interaction (NES: −2.17, p < 0.001), focal adhesion (NES: −2.02, p < 0.001), and actin cytoskeleton regulation (NES: −1.73, p < 0.001) ( Figure 3 D).…”

Loss of IRF7 accelerates acute myeloid leukemia progression and induces VCAM1-VLA-4 mediated intracerebral invasion

“…IRF7 has been implicated in tumor progression and microenvironment-related mechanisms have been proposed [ 16 , 31 ], while opposite intrinsic effects on tumor progression were reported in different tumors [ 17 , 18 ]. In hematopoiesis, IRF7 promotes the proliferation of HSCs under stress conditions [ 32 ]. Downregulation of IRF7 was detected in some AML cases with specific genetic abnormalities from Bloodspot.…”

Promotive role of IRF7 in ferroptosis of colonic epithelial cells in ulcerative colitis by the miR-375-3p/SLC11A2 axis

“…Existing studies have demonstrated the multifaceted roles of IRF7 in diseases by targeting downstream genes [ 19 , 56 ]. miR-375-3p upregulation is deemed to reduce the production of IL-1β and IL-6 in ECs in atopic dermatitis [ 57 ], and miR-375-3p upregulation in endothelial progenitor cells-isolated extracellular vesicles ameliorates sepsis in rats, as evidenced by alleviated pathological damage and decreased apoptosis, inflammatory responses, and oxidative stress in rat myocardial tissue [ 58 ], indicating the beneficial role of miR-375-3p in cell survival.…”

“…IRF7, as a transcription factor, functions in disease by targeting downstream genes [ 19 ]. microRNAs (miRs), a subcategory of noncoding RNAs, affect gene expression at the post-transcriptional level by interacting with the target messenger RNAs (mRNAs) and act as regulators of cellular processes and animal development [ 20 ].…”