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bioRxiv · 10.1101/534859

The lymphoid-associated interleukin 7 receptor (IL-7R) regulates tissue resident macrophage development

Leung, G.·Cool, T.·Valencia, C.·Worthington, A.·Beaudin, A.·Forsberg, C.
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Abstract

The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search for the mechanisms underlying their development. Here, we performed in vivo lineage tracing of cells with an expression history of IL-7R, a marker exclusively associated with the lymphoid lineage in adult hematopoiesis. Surprisingly, we found that IL7R-Cre labeled fetal-derived, adult trMacs. Labeling was almost complete in some tissues and partial in other organs. The putative progenitors of trMacs, yolk sac (YS) erythromyeloid progenitors (EMPs), did not express IL-7R, and YS hematopoiesis was unperturbed in IL-7R-deficient mice. In contrast, tracking of IL-7R message levels, surface protein expression, and IL7R-Cre-mediated labeling across fetal development revealed dynamic regulation of IL-7R mRNA expression and rapid upregulation of IL-7R surface protein upon transition from monocyte to macrophage within fetal tissues. Fetal liver monocyte differentiation in vitro produced IL-7R+ macrophages, supporting a direct progenitor-progeny relationship. Additionally, blockade of IL-7R function during late gestation specifically impaired the establishment of fetal-derived tissue macrophages in vivo. These data provide evidence for a distinct function of IL-7R in fetal myelopoiesis and identify IL-7R as a novel regulator of tissue-resident macrophage development.

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Leung, G., Cool, T., Valencia, C., Worthington, A., Beaudin, A., Forsberg, C.. 2019-01-30. The lymphoid-associated interleukin 7 receptor (IL-7R) regulates tissue resident macrophage development. https://doi.org/10.1101/534859

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