Journal article

Inhibitor of Apoptosis Proteins (IAPs) Limit RIPK1-Mediated Skin Inflammation

Holly Anderton, James A Rickard, George A Varigos, Najoua Lalaoui, John Silke

JOURNAL OF INVESTIGATIVE DERMATOLOGY | ELSEVIER SCIENCE INC | Published : 2017

Abstract

Inhibitor of apoptosis proteins (IAPs) are critical regulators of cell death and survival pathways. Mice lacking cIAP1 and either cIAP2 or XIAP die in utero, and myeloid lineage-specific deletion of all IAPs causes sterile inflammation, but their role in the skin is unknown. We generated epidermal-specific IAP-deficient mice and found that combined genetic deletion of cIAP1 (epidermal knockout [EKO]) in keratinocytes and ubiquitous cIAP2 deletion (cIap1EKO/EKO.cIap2-/-) caused profound skin inflammation and keratinocyte death, lethal by postpartum day 10. To investigate their role in skin homeostasis, we injected an IAP antagonist compound subcutaneously into wild-type and knockout mice. Thi..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Victorian State Government Operational Infrastructure Support, Australian Government NHMRC Independent Research Institute


Awarded by NHMRC


Funding Acknowledgements

We thank the staff of the WEHI Bioservices and histology facilities for practical assistance and the Thomas William Francis and Violet Coles Trust for support. This work was funded by National Health and Medical Research Council (NHMRC) grants 1025594, 1046984, and 1081221 and was made possible through Victorian State Government Operational Infrastructure Support, Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme (9000220), an Australian Government Research Training Program Scholarship, and NHMRC scholarship 1093637.