Deletion of IKK2 in haematopoietic cells of adult mice leads to elevated interleukin-6, neutrophilia and fatal gastrointestinal inflammation

Fischer, KC; Daunt, CP; Tremblay, CS; Dias, S; Vince, JE; Jabbour, AM

Author(s): Fischer, KC; Daunt, CP; Tremblay, CS; Dias, S; Vince, JE; Jabbour, AM;
Details: Publication Year 2021-01-04,Volume 12,Issue #1,Page 28
Journal Title: Cell death & Disease
Abstract: The IκB kinase complex, consisting of IKK1, IKK2 and the regulatory subunit NEMO, is required for NF-κB signalling following the activation of several cell surface receptors, such as members of the Tumour Necrosis Factor Receptor superfamily and the Interleukin-1 Receptor. This is critical for haematopoietic cell proliferation, differentiation, survival and immune responses. To determine the role of IKK in the regulation of haematopoiesis, we used the Rosa26(Cre-ERT2) Cre/lox recombination system to achieve targeted, haematopoietic cell-restricted deletion of the genes for IKK1 or IKK2 in vivo. We found that the IKK complex plays a critical role in haematopoietic cell development and function. Deletion of IKK2, but not loss of IKK1, in haematopoietic cells led to an expansion of CD11b/Gr-1-positive myeloid cells (neutrophilia), severe anaemia and thrombocytosis, with reduced numbers of long-term haematopoietic stem cells (LT-HSCs), short-term haematopoietic stem cells (ST-HSCs) and multipotential progenitor cells (MPPs), increased circulating interleukin-6 (IL-6) and severe gastrointestinal inflammation. These findings identify distinct functions for the two IKK catalytic subunits, IKK1 and IKK2, in the haematopoietic system.
Publisher: NPG
Research Division(s): Blood Cells And Blood Cancer; Inflammation
PubMed ID: 33414459
Publisher's Version: https://doi.org/10.1038/s41419-020-03298-9
Open Access at Publisher's Site: https://doi.org/10.1038/s41419-020-03298-9
NHMRC Grants: NHMRC/1145788, NHMRC/1101405, NHMRC/1183070, NHMRC/1141466,
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41419-020-03298-9.pdf - (3.13MB, application/pdf)

Creation Date: 2021-03-04 09:10:11

Last Modified: 2021-03-08 11:33:20