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

Ki Wook Kim, Jesse W. Williams, Ya Ting Wang, Stoyan Ivanov, Susan Gilfillan, Marco Colonna, Herbert W. Virgin, Emmanuel L. Gautier, Gwendalyn J. Randolph

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80 + macrophages and MHC II + CD11c + macrophages. F4/80 + macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II + macrophages remain unknown. Here, we show that the MHC II + macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes. Monocytes continuously replenish this subset through adulthood. Gene expression analysis identified distinct surface markers like CD226 and revealed that the transcription factor IRF4 was selectively expressed in these macrophages relative to other organs. Monocytes first entered peritoneal or pleural cavities to become MHC II+ cells that up-regulated CD226 and CD11c later as they continued to mature. In the absence of IRF4 or after administration of oral antibiotics, MHC II + CD226 - CD11c - monocyte-derived cells accumulated in peritoneal and pleural cavities, but CD11c + CD226 + macrophages were lost. Thus, MHC II + resident peritoneal and pleural macrophages are continuously replenished by blood monocytes recruited to the peritoneal and pleural cavities constitutively, starting after birth, where they require IRF4 and signals likely derived from the microbiome to fully differentiate.

Original languageEnglish (US)
Pages (from-to)1951-1959
Number of pages9
JournalJournal of Experimental Medicine
Issue number10
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) grants R01 AI049653, R21 AG046734, R01 HL118206, and DP1DK109668 to G.J. Randolph. J.W. Williams was supported by NIH training grant 2T32DK007120-41.

Publisher Copyright:
© 2016 Kim et al.


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