Authors
Jichang Han, Alexandre Gallerand, Rachel L Mintz, Jing Chen, Feiya Ou, Shuai Gao, Daniel D Lee, Mandy M Chan, Michael T Harmon, Xue Lin, Bhama Ramkhelawon, Christopher G Huckstep, Michael R Strickland, Tiantian Liu, Kory J Lavine, Joel D Schilling, S Celeste Morley, Bernd H Zinselmeyer, Kenneth M Murphy, Gwendalyn J Randolph
Published in
Science immunology. Volume 11. Issue 121. Pages eaeg8653. Jul 31, 2026. Epub Jul 31, 2026.
Abstract
Peritoneal cavity fluid and mesothelial surfaces host distinct resident macrophage populations, among which include the well-described Gata6+ large cavity macrophages (LCMs) in peritoneal fluid. Here, we reveal that LCMs arise from two separable differentiation pathways. In the quantitatively minor pathway, monocytes gave rise to LYVE1+ LCMs but few Gata6+ LCMs. This pathway did not require the transcription factor Gata6 but was severely impaired in mice bearing three mutations in the -165 kb Zeb2 enhancer (Zeb2TM) with impaired monocyte development. The second, dominant pathway supported Gata6-dependent LCMs and was intact in Zeb2TM mice, even when turnover was enforced by irradiation, and was supported by adoptive transfer of a specialized LCM intermediate expressing Gata6 before the residency marker TIMD4. Functionally, the quantitatively minor LCM pathway distinctly surveilled the mesothelium, replenishing mesothelial border macrophages upon encountering an open niche. Thus, beyond embryonic versus adult hematopoietic paradigms, LCMs with overlapping and distinct phenotypes arise from two pathways linked to divergent fates.
PMID:
42536710
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.
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