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| Status |
Public on Dec 01, 2012 |
| Title |
Genome-wide analysis of gene expression in Krt1+/+ versus Krt1-/- epidermis and full-thickness skin. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) constitute the intermediate filament cytoskeleton of suprabasal skin keratinocytes. They participate in formation of the epidermal barrier, which protects against dehydration and inflammation. Mutations in KRT1 cause keratinopathic ichthyosis with erythema, recurrent inflammation, and barrier defects. Here, we show that genetic deletion of Krt1 in mice causes a defective inside-out epidermal barrier, pre- and postnatal increases in Mrp8/Mrp14, interleukin (IL) 18, IL-33, and thymic stromal lymphopoietin (TSLP) in skin extracts, and systemic release of IL-18 into newborn serum. Perinatal lethality was partially rescued by treatment with glucocorticoids to promote barrier repair or with IL- 18-blocking antibodies in utero. In human keratinocytes, IL-18 release was cellautonomous and caspase-1-dependent, indicating KRT1-dependent inflammasome activation. Our data reveal a novl function of KRT1 in controlling inflammasome activity and stimulating barrier formation, thereby integrating the keratin cytoskeleton into the epidermal immune response. In view of their widespread expression, keratins merit investigation of their functions in inflammatory conditions, including asthma and inflammatory bowel disorders.
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| Overall design |
Total RNA was obtained from epidermis or full-thickness skin of Krt1+/+ and Krt1-/- mice (C57BL/6 background) at P0 (newborn).
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| Contributor(s) |
Roth W, Margin T, Staratschek-Jox A, Schultze JL |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 13, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
j.schultze@uni-bonn.de
|
| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
|
| Department |
Genomics and Immunoregulation
|
| Street address |
Carl-Troll-Strasse 31
|
| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
|
| Samples (12)
|
| GSM815914 |
newborn (P0) Krt1+/+ epidermis_replicate 1 |
| GSM815915 |
newborn (P0) Krt1-/- skin_replicate 1 |
| GSM815916 |
newborn (P0) Krt1-/- skin_replicate 2 |
| GSM815917 |
newborn (P0) Krt1+/+ epidermis_replicate 2 |
| GSM815918 |
newborn (P0) Krt1-/- skin_replicate 3 |
| GSM815919 |
newborn (P0) Krt1+/+ epidermis_replicate 3 |
| GSM815920 |
newborn (P0) Krt1-/- epidermis_replicate 1 |
| GSM815921 |
newborn (P0) Krt1+/+ skin_replicate 1 |
| GSM815922 |
newborn (P0) Krt1+/+ skin_replicate 2 |
| GSM815923 |
newborn (P0) Krt1-/- epidermis_replicate 2 |
| GSM815924 |
newborn (P0) Krt1-/- epidermis_replicate 3 |
| GSM815925 |
newborn (P0) Krt1+/+ skin_replicate 3 |
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| Relations |
| BioProject |
PRJNA146469 |
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