MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes

Area of Science:

• Immunology
• Cell Biology
• Microbiome Research

Background:

• Peritoneal and pleural cavities harbor two resident macrophage subsets: F4/80(+) and MHC II(+) CD11c(+).
• F4/80(+) macrophages originate from embryonic precursors regulated by Gata6.
• The origin and maintenance mechanisms for MHC II(+) macrophages remain largely unknown.

Purpose of the Study:

• To elucidate the origin and regulatory factors of MHC II(+) resident macrophages in the peritoneal and pleural cavities.
• To investigate the role of monocytes and specific transcription factors in the maintenance of these macrophage populations.

Main Methods:

• Analysis of macrophage subpopulations using surface markers (F4/80, MHC II, CD11c, CD226).
• Investigated monocyte recruitment and differentiation pathways.
• Utilized gene expression analysis and transcription factor (IRF4) knockout models.
• Assessed the impact of oral antibiotics on macrophage populations.

Main Results:

• MHC II(+) macrophages arise postnatally from CCR2-dependent monocyte precursors.
• Blood monocytes continuously replenish this subset throughout adulthood.
• IRF4 is selectively expressed in these macrophages, and its absence leads to accumulation of immature MHC II(+)CD226(-)CD11c(-) cells and loss of mature CD11c(+) CD226(+) macrophages.
• Oral antibiotics disrupt the differentiation of MHC II(+) macrophages.

Conclusions:

• MHC II(+) resident peritoneal and pleural macrophages are continuously replenished by blood monocytes.
• This differentiation process requires the transcription factor IRF4 and signals potentially derived from the microbiome.
• Monocyte recruitment and subsequent differentiation are critical for maintaining the mature MHC II(+) macrophage population.