Journal article

cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1-and RIPK3-dependent manner

W Wei-Lynn Wong, James E Vince, Najoua Lalaoui, Kate E Lawlor, Diep Chau, Aleksandra Bankovacki, Holly Anderton, Donald Metcalf, Lorraine O'Reilly, Philipp J Jost, James M Murphy, Warren S Alexander, Andreas Strasser, David L Vaux, John Silke

BLOOD | AMER SOC HEMATOLOGY | Published : 2014

Abstract

Loss of inhibitor of apoptosis proteins (IAPs), particularly cIAP1, can promote production of tumor necrosis factor (TNF) and sensitize cancer cell lines to TNF-induced necroptosis by promoting formation of a death-inducing signaling complex containing receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3. To define the role of IAPs in myelopoiesis, we generated a mouse with cIAP1, cIAP2, and XIAP deleted in the myeloid lineage. Loss of cIAPs and XIAP in the myeloid lineage caused overproduction of many proinflammatory cytokines, resulting in granulocytosis and severe sterile inflammation. In vitro differentiation of macrophages from bone marrow in the absence of cIAPs and XIAP..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Leukemia and Lymphoma Society and NHMRC


Awarded by Swiss National Science Foundation


Awarded by NHMRC


Awarded by Australian Research Council Future Fellowship


Awarded by Australian Government NHMRC Institutional Research Interactive Information System


Funding Acknowledgements

This work was supported by grants from National Health and Medical Research Council (NHMRC) (433013, 356256, and 461221) (J.S.), NHMRC Australian Fellowships and Leukemia and Lymphoma Society and NHMRC (461221) grants (D. L. V. and A. S.), Swiss National Science Foundation (310030_138085/1) (W. W.-L. W.), NHMRC grant (1051210) (J.E.V. and K. E. L.), an NHMRC Career Development Fellowship (1052598) (J.E.V.), an Australian Research Council Future Fellowship (FT100100100) and NHMRC grant (637342) (J.M.M.), NHMRC Program grant (1016647) and Research Fellowship (575501) (W. S. A.), the Leukemia and Lymphoma Society and an NHMRC project grant (1009145) (L.O.), the Cancer Council Victoria (D. M.), and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Institutional Research Interactive Information System (361646).