Universität zu Köln

Bonnet, Marion C., Preukschat, Daniela, Welz, Patrick-Simon ORCID: 0000-0001-8370-625X, van Loo, Geert, Ermolaeva, Maria A., Bloch, Wilhelm, Haase, Ingo and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2011). The Adaptor Protein FADD Protects Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation. Immunity, 35 (4). S. 572 - 583. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Epidermal keratinocytes provide an essential structural and immunological barrier forming the first line of defense against potentially pathogenic microorganisms. Mechanisms regulating barrier integrity and innate immune responses in the epidermis are important for the maintenance of skin immune homeostasis and the pathogenesis of inflammatory skin diseases. Here, we show that epidermal keratinocyte-restricted deficiency of the adaptor protein FADD (FADD(E-KO)) induced severe inflammatory skin lesions in mice. The development of skin inflammation in FADD(E-KO) mice was triggered by RIP kinase 3 (RIP3)-mediated programmed necrosis (termed necroptosis) of FADD-deficient keratinocytes, which was partly dependent on the deubiquitinating enzyme CYLD and tumor necrosis factor (TNF)-TNF receptor 1 signaling. Collectively, our findings provide an in vivo experimental paradigm that regulation of necroptosis in keratinocytes is important for the maintenance of immune homeostasis and the prevention of chronic inflammation in the skin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bonnet, Marion C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Preukschat, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Welz, Patrick-Simon UNSPECIFIED orcid.org/0000-0001-8370-625X UNSPECIFIED van Loo, Geert UNSPECIFIED UNSPECIFIED UNSPECIFIED Ermolaeva, Maria A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Haase, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-486959
DOI:	10.1016/j.immuni.2011.08.014
Journal or Publication Title:	Immunity
Volume:	35
Number:	4
Page Range:	S. 572 - 583
Date:	2011
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECEPTOR-INTERACTING PROTEIN; CELL-DEATH; TARGETED DISRUPTION; PROGRAMMED NECROSIS; B-CELL; MICE; IMMUNE; INHIBITION; IDENTIFICATION; REQUIREMENT Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48695