Human peritoneal CCR2^LowCRIg^High macrophage subset exhibits embryonic origin-like phenotypes

Area of Science:

• Immunology
• Cell Biology
• Developmental Biology

Background:

• Adult tissue macrophages are traditionally thought to derive from bone marrow monocytes.
• Recent mouse studies suggest adult macrophages are also maintained by self-proliferation from embryonic progenitors.
• The presence and role of embryonic-derived macrophages in human tissues remain largely unexplored.

Purpose of the Study:

• To investigate the origin and phenotype of human peritoneal macrophages.
• To determine if embryonic-derived macrophages exist in the human peritoneal cavity.
• To characterize distinct macrophage subsets in ascites from gastric cancer patients.

Main Methods:

• Analysis of macrophage subsets in ascites from gastric cancer patients.
• Flow cytometry and gene expression profiling to distinguish macrophage subsets (CCR2^Low/^High, CRIg^High/^Low).
• Assessment of cell proliferation marker Ki67 and embryonic macrophage markers (TIMD4, LYVE1, FOLR2).

Main Results:

• Two peritoneal macrophage subsets, CCR2^Low and CCR2^High, were identified, with varying ratios among patients.
• The CCR2^LowCRIg^High subset showed higher expression of Ki67 and embryonic macrophage markers (TIMD4, LYVE1, FOLR2) compared to the CCR2^HighCRIg^Low subset.
• Expression patterns of multiple embryonic macrophage markers in the CCR2^LowCRIg^High subset mirrored those found in embryonic-derived macrophages in other human organs.

Conclusions:

• A subset of human peritoneal macrophages (CCR2^LowCRIg^High) exhibits phenotypes consistent with embryonic origin.
• These findings suggest that macrophages derived from embryonic progenitors may contribute to the maintenance of adult human tissues.
• This challenges the traditional view of monocyte differentiation as the sole source of adult tissue macrophages.