Unknown,Transcriptomics,Genomics,Proteomics

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Grhl3 is essential for epidermal barrier repair from both physical and immune injury, relevance to lesional skin disease


ABSTRACT: Epidermal barrier repair mechanisms activated in psoriasis lesions are likely involved in limiting the severity of this disease. We show that loss of grainyhead-like 3 (Grhl3), a pro-terminal differentiation factor in the epidermis, is sufficient to trigger greater sensitivity to and delayed resolution of epidermal lesions resulting from either physical or immune mediated barrier injury. After stimulation of Toll like receptors, the loss of Grhl3 resulted in increased epidermal damage with a striking increase in basal cell proliferation, hyperplasia of partially differentiated suprabasal layers, and a transcriptional profile highlighted by the overexpression of epidermal wound response and alarmin genes. This study reveals an important role for the epidermis in the initiation and recovery from immune-mediated lesions, and indicated that the epidermal regulator Grhl3 acts to both suppress disease initiation and resolve existing lesions. This work suggests that treatments focused on improving barrier function could be used preventatively and therapeutically in psoriasis. Whole skin was collected from E16.5 mouse backskins for Grhl3 ChIP. Adult epidermis for depilation and imiquimod experiments was seperated from dermis using dispase prior to Grhl3 ChIP.

ORGANISM(S): Mus musculus

SUBMITTER: Bogi Andersen 

PROVIDER: E-GEOD-52648 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia.

Gordon William M WM   Zeller Michael D MD   Klein Rachel H RH   Swindell William R WR   Ho Hsiang H   Espetia Francisco F   Gudjonsson Johann E JE   Baldi Pierre F PF   Andersen Bogi B  

The Journal of clinical investigation 20141027 12


Dermal infiltration of T cells is an important step in the onset and progression of immune-mediated skin diseases such as psoriasis; however, it is not known whether epidermal factors play a primary role in the development of these diseases. Here, we determined that the prodifferentiation transcription factor grainyhead-like 3 (GRHL3), which is essential during epidermal development, is dispensable for adult skin homeostasis, but required for barrier repair after adult epidermal injury. Consiste  ...[more]

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