NEUROTROPIC CALCERGY.

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<b>BACKGROUND</b> 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. <b>METHODS</b> Mice carrying <i>loxP</i>-flanked IKKβ alleles (IKKβ^fl/fl) were crossed with Vav1-iCre mice to target IKKβ expression in hematopoietic cells (IKKβ^Δ/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. <b>RESULTS</b> IKKβ^Δ/fl mice are phenotypically indistinguishable from IKKβ^fl/fl (WT) mice. In contrast, IKKβ^Δ/Δ mice are born in non-Mendelian ratios, develop patchy alopecia, osteopetrosis, splenomegaly and stunted growth. IKKβ^Δ/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 IKKβ^Δ/fl and WT controls. Unlike in IKKβ^Δ/fl or WT granulocyte macrophage progenitors (GMP), IKKβ^Δ/Δ GMPs proliferate more in response to G-CSF than to GM-CSF or IL-3 stimulation. Moreover, G-CSF stimulated IKKβ^Δ/Δ MP produce more neutrophils relative to IKKβ^Δ/fl and WT MP. <b>CONCLUSIONS</b> Our data indicate that IKKβ controls homeostatic granulopoiesis through regulating sensitivity to G-CSF signals in MP.