Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo

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Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo. / Romanowska, Malgorzata; Reilly, Louise; Palmer, Colin; Gustafsson, Mattias; Foerster, John.

In: PLoS ONE, Vol. 5, No. 3, e9701, 2010.

Research output: Contribution to journalArticle

Harvard

Romanowska, M, Reilly, L, Palmer, C, Gustafsson, M & Foerster, J 2010, 'Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo', PLoS ONE, vol. 5, no. 3, e9701. https://doi.org/10.1371/journal.pone.0009701

APA

Romanowska, M., Reilly, L., Palmer, C., Gustafsson, M., & Foerster, J. (2010). Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo. PLoS ONE, 5(3), [e9701]. https://doi.org/10.1371/journal.pone.0009701

CBE

Romanowska M, Reilly L, Palmer C, Gustafsson M, Foerster J. 2010. Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo. PLoS ONE. 5(3):Article e9701. https://doi.org/10.1371/journal.pone.0009701

MLA

Vancouver

Romanowska M, Reilly L, Palmer C, Gustafsson M, Foerster J. Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo. PLoS ONE. 2010;5(3). e9701. https://doi.org/10.1371/journal.pone.0009701

Author

Romanowska, Malgorzata ; Reilly, Louise ; Palmer, Colin ; Gustafsson, Mattias ; Foerster, John. / Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo. In: PLoS ONE. 2010 ; Vol. 5, No. 3.

RIS

TY - JOUR

T1 - Activation of PPARβ/δ Causes a Psoriasis-Like Skin Disease In Vivo

AU - Romanowska, Malgorzata

AU - Reilly, Louise

AU - Palmer, Colin

AU - Gustafsson, Mattias

AU - Foerster, John

PY - 2010

Y1 - 2010

N2 - Background: Psoriasis is one of the most frequent skin diseases world-wide. The disease impacts enormously on affected patients and poses a huge financial burden on health care providers. Several lines of evidence suggest that the nuclear hormone receptor peroxisome proliferator activator (PPAR) beta/delta, known to regulate epithelial differentiation and wound healing, contributes to psoriasis pathogenesis. It is unclear, however, whether activation of PPAR beta/delta is sufficient to trigger psoriasis-like changes in vivo. Methodology/Principal Findings: Using immunohistochemistry, we define the distribution of PPAR beta/delta in the skin lesions of psoriasis. By expression profiling, we confirm that PPAR beta/delta is overexpressed in the vast majority of psoriasis patients. We further establish a transgenic model allowing inducible activation of PPAR beta/delta in murine epidermis mimicking its distribution in psoriasis lesions. Upon activation of PPAR beta/delta, transgenic mice sustain an inflammatory skin disease strikingly similar to psoriasis, featuring hyperproliferation of keratinocytes, dendritic cell accumulation, and endothelial activation. Development of this phenotype requires the activation of the Th17 subset of T cells, shown previously to be central to psoriasis. Moreover, gene dysregulation in the transgenic mice is highly similar to that in psoriasis. Key transcriptional programs activated in psoriasis, including IL1-related signalling and cholesterol biosynthesis, are replicated in the mouse model, suggesting that PPAR beta/delta regulates these transcriptional changes in psoriasis. Finally, we identify phosphorylation of STAT3 as a novel pathway activated by PPAR beta/delta and show that inhibition of STAT3 phosphorylation blocks disease development. Conclusions: Activation of PPAR beta/delta in the epidermis is sufficient to trigger inflammatory changes, immune activation, an

AB - Background: Psoriasis is one of the most frequent skin diseases world-wide. The disease impacts enormously on affected patients and poses a huge financial burden on health care providers. Several lines of evidence suggest that the nuclear hormone receptor peroxisome proliferator activator (PPAR) beta/delta, known to regulate epithelial differentiation and wound healing, contributes to psoriasis pathogenesis. It is unclear, however, whether activation of PPAR beta/delta is sufficient to trigger psoriasis-like changes in vivo. Methodology/Principal Findings: Using immunohistochemistry, we define the distribution of PPAR beta/delta in the skin lesions of psoriasis. By expression profiling, we confirm that PPAR beta/delta is overexpressed in the vast majority of psoriasis patients. We further establish a transgenic model allowing inducible activation of PPAR beta/delta in murine epidermis mimicking its distribution in psoriasis lesions. Upon activation of PPAR beta/delta, transgenic mice sustain an inflammatory skin disease strikingly similar to psoriasis, featuring hyperproliferation of keratinocytes, dendritic cell accumulation, and endothelial activation. Development of this phenotype requires the activation of the Th17 subset of T cells, shown previously to be central to psoriasis. Moreover, gene dysregulation in the transgenic mice is highly similar to that in psoriasis. Key transcriptional programs activated in psoriasis, including IL1-related signalling and cholesterol biosynthesis, are replicated in the mouse model, suggesting that PPAR beta/delta regulates these transcriptional changes in psoriasis. Finally, we identify phosphorylation of STAT3 as a novel pathway activated by PPAR beta/delta and show that inhibition of STAT3 phosphorylation blocks disease development. Conclusions: Activation of PPAR beta/delta in the epidermis is sufficient to trigger inflammatory changes, immune activation, an

U2 - 10.1371/journal.pone.0009701

DO - 10.1371/journal.pone.0009701

M3 - Article

C2 - 20300524

VL - 5

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e9701

ER -