uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Tumor Necrosis Factor Receptor Signaling in Keratinocytes Triggers Interleukin-24-Dependent Psoriasis-like Skin Inflammation in Mice
Karolinska Institutet. (Taija Mäkinen)
Show others and affiliations
2013 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 5, no 39, 899-911 p.Article in journal (Refereed) Published
Abstract [en]

Psoriasis is a common chronic inflammatory skin disease with a prevalence of about 2% in the Caucasian population. Tumor necrosis factor (TNF) plays an essential role in the pathogenesis of psoriasis, but its mechanism of action remains poorly understood. Here we report that the development of psoriasis-like skin inflammation in mice with epidermis-specific inhibition of the transcription factor NF-κB was triggered by TNF receptor 1 (TNFR1)-dependent upregulation of interleukin-24 (IL-24) and activation of signal transducer and activator of transcription 3 (STAT3) signaling in keratinocytes. IL-24 was strongly expressed in human psoriatic epidermis, and pharmacological inhibition of NF-κB increased IL-24 expression in TNF-stimulated human primary keratinocytes, suggesting that this mechanism is relevant for human psoriasis. Therefore, our results expand current views on psoriasis pathogenesis by revealing a new keratinocyte-intrinsic mechanism that links TNFR1, NF-κB, ERK, IL-24, IL-22R1, and STAT3 signaling to disease initiation.

Place, publisher, year, edition, pages
2013. Vol. 5, no 39, 899-911 p.
Keyword [en]
Psoriasis, NFkappaB, TNF, inflammation, skin, IL-24
National Category
Medical and Health Sciences
Research subject
Medical Science
URN: urn:nbn:se:uu:diva-220607DOI: 10.1016/j.immuni.2013.10.009.OAI: oai:DiVA.org:uu-220607DiVA: diva2:705785
Available from: 2014-03-17 Created: 2014-03-17 Last updated: 2014-03-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 190 hits
ReferencesLink to record
Permanent link

Direct link