Keratin 1 maintains skin integrity and participates in an inflammatory network in skin through interleukin-18

被引：146

作者：

Roth, Wera ^{[1
,2
]}

Kumar, Vinod ^{[1
,2
]}

Beer, Hans-Dietmar ^{[3
]}

Richter, Miriam ^{[1
,2
]}

Wohlenberg, Claudia ^{[4
]}

Reuter, Ursula ^{[4
]}

Thiering, Soeren ^{[1
,2
]}

Staratschek-Jox, Andrea ^{[5
]}

Hofmann, Andrea ^{[5
]}

Kreusch, Fatima ^{[5
]}

Schultze, Joachim L. ^{[5
]}

Vogl, Thomas ^{[6
]}

Roth, Johannes ^{[6
]}

Reichelt, Julia ^{[7
,8
]}

Hausser, Ingrid ^{[9
]}

Magin, Thomas M. ^{[1
,2
]}

机构：

[1] Univ Leipzig, Translat Ctr Regenerat Med TRM, D-04103 Leipzig, Germany

[2] Univ Leipzig, Inst Biol, D-04103 Leipzig, Germany

[3] Univ Zurich, Dept Dermatol, Univ Hosp, CH-8006 Zurich, Switzerland

[4] Univ Bonn, Inst Biochem & Mol Biol, Div Cell Biochem, D-53115 Bonn, Germany

[5] Univ Bonn, LIMES Inst, Dept Genom & Immunoregulat, D-53115 Bonn, Germany

[6] Univ Munster, Inst Immunol, D-48149 Munster, Germany

[7] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[8] Newcastle Univ, NE England Stem Cell Inst, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[9] Heidelberg Univ, Univ Hautklin, D-69120 Heidelberg, Germany

来源：

JOURNAL OF CELL SCIENCE | 2012年 / 125卷 / 22期

关键词：

Keratin cytoskeleton; Epidermal barrier; Innate immunity; Interleukin-18; Atopic eczema; EPIDERMOLYSIS-BULLOSA SIMPLEX; ATOPIC-DERMATITIS; NULL MICE; STRATUM-CORNEUM; INNATE IMMUNITY; IN-VITRO; BARRIER; EXPRESSION; MUTATIONS; FILAGGRIN;

D O I：

10.1242/jcs.116574

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis. KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation control, we show here that Krt1 is crucial for maintenance of skin integrity and participates in an inflammatory network in murine keratinocytes. Absence of Krt1 caused a prenatal increase in interleukin-18 (IL-18) and the S100A8 and S100A9 proteins, accompanied by a barrier defect and perinatal lethality. Depletion of IL-18 partially rescued Krt1(-/-) mice. IL-18 release was keratinocyte-autonomous, KRT1 and caspase-1 dependent, supporting an upstream role of KRT1 in the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene expression signature similar to atopic eczema and psoriasis, but different from Krt5 deficiency and epidermolysis bullosa simplex. Our data suggest a functional link between KRT1 and human inflammatory skin diseases.

引用

页码：5269 / 5279

页数：11

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