Tissue resident macrophages regulate IL‐23‐dependent granulopoiesis (146.7)

Mice deficient in α(1,3)‐fucosyltransferases 4 and 7 (FUT‐/‐) lack selectin ligand activity and selectin‐dependent leukocyte trafficking, resulting in altered IL‐23‐dependent granulopoiesis. It is not clear if this granulopoiesis is regulated by bone marrow‐derived macrophages (BMMC) or a distinct population of tissue resident macrophages (TRM). We hypothesized that the loss of FUT‐dependent trafficking reduces the number of neutrophils able to infiltrate tissues, undergo apoptosis, and be phagocytosed by TRMs, altering IL‐23 production. Primary Kupffer cells (pKC) and BMMC were isolated from FUT‐/‐ and WT mice, stimulated in vitro with LPS, and assessed for IL‐23 production. WT mice were irradiated and their hematopoietic system was reconstituted with 1x106 bone marrow cells isolated from WT or FUT‐/‐ mice. Six weeks after reconstitution, circulating WBC counts were assessed. There was no difference in gene expression levels of IL‐23 between WT and FUT‐/‐ pKCs or BMMCs, indicating that IL‐23 production from FUT‐/‐ macrophages is intact. WT mice reconstituted with FUT‐/‐ bone marrow show a pronounced neutrophilia similar to that seen in FUT‐/‐ mice. These results confirm that FUT‐dependent neutrophil trafficking is required for the regulation of granulopoiesis and suggest that the TRM populations are responsible for clearing apoptotic neutrophils and regulating IL‐23 production in granulopoiesis. Grant Funding Source : R01‐HL090823, T32‐HL069768