Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

Area of Science:

• Immunology
• Cell Biology
• Hematology

Background:

• Tissue-resident macrophages, crucial for organ function, were traditionally believed to originate solely from embryonic progenitors.
• The potential contribution of circulating monocytes to self-renewing tissue-resident macrophage populations remained largely uninvestigated.

Purpose of the Study:

• To investigate whether circulating monocytes can differentiate into self-renewing tissue-resident macrophages.
• To explore the role of niche availability in monocyte-derived macrophage engraftment and self-renewal.

Main Methods:

• A novel diphtheria toxin-based model was employed to deplete liver-resident Kupffer cells, creating available niches.
• Engraftment, transcriptional profiling, and long-term self-renewal capacity of circulating monocytes in the liver were assessed.

Main Results:

• Circulating monocytes successfully engrafted into the liver following Kupffer cell depletion.
• Engrafted monocytes gradually acquired the transcriptional identity of resident Kupffer cells.
• These monocyte-derived macrophages demonstrated long-term self-renewal capabilities.
• Monocytes also contributed to the liver macrophage pool during neonatal development, coinciding with natural niche expansion.

Conclusions:

• Circulating monocytes are a viable source of self-renewing tissue-resident macrophages, provided a suitable niche is available.
• This finding expands our understanding of macrophage ontogeny and homeostasis.
• Monocyte-derived macrophages play a significant role in replenishing tissue macrophage populations, particularly during development and in response to injury or depletion.