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- W4313354749 abstract "Abstract BACKGROUND IL-1β-mediated neutrophilia has been observed in mice with an inducible deletion of IKKβ under non-homeostatic conditions. We investigated the effects of a constitutive IKKβ deletion from the hematopoietic compartment. METHODS Mice carrying loxP-flanked IKKβ alleles (IKKβfl/fl) were crossed with Vav1-iCre mice to target IKKβ expression in hematopoietic cells (IKKβΔ/Δ). Bone marrow (BM), blood, spleen and peripheral tissues were analyzed by histopathology and FACS. Methylcellulose colony-forming cell (CFU) assays were performed using Lin-c-kit+ myeloid progenitors (MP) and splenocytes. MP proliferation was measured by EdU incorporation. RESULTS IKKβΔ/fl mice are phenotypically indistinguishable from IKKβfl/fl (WT) mice. In contrast, IKKβΔ/Δ mice are born in non-Mendelian ratios, develop patchy alopecia, osteopetrosis, splenomegaly and stunted growth. IKKβΔ/Δ mice also show massive neutrophilia in BM, spleen, blood and peripheral tissues as well as a sharp increase in BM and spleen granulocyte CFUs relative to IKKβΔ/fl and WT controls. Unlike in IKKβΔ/fl or WT granulocyte macrophage progenitors (GMP), IKKβΔ/Δ GMPs proliferate more in response to G-CSF than to GM-CSF or IL-3 stimulation. Moreover, G-CSF stimulated IKKβΔ/Δ MP produce more neutrophils relative to IKKβΔ/fl and WT MP. CONCLUSIONS Our data indicate that IKKβ controls homeostatic granulopoiesis through regulating sensitivity to G-CSF signals in MP." @default.
- W4313354749 created "2023-01-06" @default.
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- W4313354749 date "2013-05-01" @default.
- W4313354749 modified "2023-09-27" @default.
- W4313354749 title "Loss of homeostatic granulopoiesis in IKKβ-deficient mice (P4472)" @default.
- W4313354749 doi "https://doi.org/10.4049/jimmunol.190.supp.52.53" @default.
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