IL-1β expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function

Area of Science:

• Hematology
• Immunology
• Cell Biology

Background:

• Hematopoietic stem/progenitor cells (HSPCs) are regulated by bone marrow niches.
• Environmental cues, like inflammation, influence hematopoiesis.
• Mechanisms of cue transmission to HSPCs within niches are unclear.

Purpose of the Study:

• Investigate the role of dendritic cells (DCs) in transmitting inflammatory signals to HSPCs.
• Elucidate the signaling pathways involved in DC-mediated regulation of HSPCs.

Main Methods:

• Utilized mouse models with specific gene deletions (Myd88 in DCs, IL-1 receptor knockout).
• Administered Toll-like receptor (TLR) 1/2 agonists systemically.
• Performed single-cell RNA-sequencing on myelodysplastic syndrome bone marrow.

Main Results:

• TLR1/2 stimulation of DCs induced HSPC expansion and mobilization, altering the bone marrow microenvironment.
• DC-specific TLR1/2 signaling was crucial for HSPC expansion but not mobilization.
• TLR1/2-induced HSPC expansion depended on IL-1β signaling.
• Increased IL1B and TLR1 expression was observed in DCs from myelodysplastic syndrome patients.

Conclusions:

• TLR1/2 signaling in perivascular DCs promotes HSPC expansion via IL-1β secretion.
• This DC-TLR-IL-1β axis regulates HSPCs within the bone marrow niche.
• Dysregulated DC TLR1/2 signaling may contribute to altered HSPC function in myelodysplastic syndromes.