Skip to content Skip to navigation

MCB Seminar (4/17/18)

April 17, 2018 - 4:00pm

"IL7R Regulates Fetal Tissue Resident Macrophage Development"

Gabriel Leung, University of California, Merced

Abstract: 

macrophages play critical roles in tissue homeostasis and disease. Many populations of tissue-resident macrophages derive from fetal progenitors and self-maintain across the lifespan through in situ proliferation, independent of bone marrow hematopoiesis. However, the developmental mechanisms that specify fetal-derived tissue-resident macrophages are poorly understood. Here, we have identified a novel cytokine regulating tissue-resident macrophage development using an IL7Ra-cre lineage tracing model. Adult tissue resident macrophages in the brain, skin, liver, and lung were extensively labeled by IL7ra-cre, in the absence of IL7ra message or protein expression. To gain insight into developmental expression of IL7ra, we profiled IL7Ra surface expression, mRNA expression, and IL7ra-cre-driven labeling across fetal myeloid development. We observed rapid upregulation of IL7ra surface expression during a limited window of tissue macrophage establishment, and dynamic regulation of IL7ra message and protein levels in monocyte precursors, suggesting that IL7ra regulated the transition from fetal liver monocytes into tissue macrophages. Blockade of the IL7R using a monoclonal antibody decreased cellularity of liver, lung and skin tissue resident macrophages at birth, and increased cellularity of fetal liver monocytes. These data suggest that late in gestation, IL7Ra is upregulated as fetal monocytes exit the fetal liver and differentiate into macrophages, and provides evidence that IL-7R signaling regulates fetal tissue-resident macrophage development. Ongoing work addresses the function of IL-7 signaling in myeloid development, and the function of IL-7R marked macrophages in adult immunity.