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http://purl.uniprot.org/citations/29596938http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29596938http://www.w3.org/2000/01/rdf-schema#comment"

Background

A delicate balance between cell death and keratinocyte proliferation is crucial for normal skin development. Previous studies have reported that cellular FLICE (FADD-like ICE)-inhibitory protein plays a crucial role in prevention of keratinocytes from TNF-α-dependent apoptosis and blocking of dermatitis. However, a role for cellular FLICE-inhibitory protein in TNF-α-independent cell death remains unclear.

Objective

We investigated contribution of TNF-α-dependent and TNF-α-independent signals to the development of dermatitis in epidermis-specific Cflar-deficient (CflarE-KO) mice.

Methods

We examined the histology and expression of epidermal differentiation markers and inflammatory cytokines in the skin of CflarE-KO;Tnfrsf1a+/- and CflarE-KO;Tnfrsf1a-/- mice. Mice were treated with neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand to block TNF-α-independent cell death of CflarE-KO;Tnfrsf1a-/- mice.

Results

CflarE-KO;Tnfrsf1a-/- mice were born but experienced severe dermatitis and succumbed soon after birth. CflarE-KO;Tnfrsf1a+/- mice exhibited embryonic lethality caused by massive keratinocyte apoptosis. Although keratinocytes from CflarE-KO;Tnfrsf1a-/- mice still died of apoptosis, neutralizing antibodies against Fas ligand and TNF-related apoptosis-inducing ligand substantially prolonged survival of CflarE-KO;Tnfrsf1a-/- mice. Expression of inflammatory cytokines, such as Il6 and Il17a was increased; conversely, expression of epidermal differentiation markers was severely downregulated in the skin of CflarE-KO;Tnfrsf1a-/- mice. Treatment of primary keratinocytes with IL-6 and, to a lesser extent, IL-17A suppressed expression of epidermal differentiation markers.

Conclusion

TNF receptor superfamily 1 (TNFR1)-dependent or TNFR1-independent apoptosis of keratinocytes promotes inflammatory cytokine production, which subsequently blocks epidermal differentiation. Thus blockade of both TNFR1-dependent and TNFR1-independent cell death might be an alternative strategy to treat skin diseases when treatment with anti-TNF-α antibody alone is not sufficient."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2018.02.043"xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Abe R."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Hasegawa A."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Miyake S."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Nishiyama C."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Koike M."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Mikami T."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Nakano H."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Takeda J."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Piao X."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Uchiyama Y."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Miura R."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Yagita H."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Komazawa-Sakon S."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/author"Shindo R."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/pages"213-228.e10"xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/title"Blockade of TNF receptor superfamily 1 (TNFR1)-dependent and TNFR1-independent cell death is crucial for normal epidermal differentiation."xsd:string
http://purl.uniprot.org/citations/29596938http://purl.uniprot.org/core/volume"143"xsd:string
http://purl.uniprot.org/citations/29596938http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29596938
http://purl.uniprot.org/citations/29596938http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29596938
http://purl.uniprot.org/uniprot/#_A0A0A6YW46-mappedCitation-29596938http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29596938
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