Mouse models: Psoriasis: an epidermal disease after all?

Guðjónsson, Jóhann E.; Elder, James T.

doi:10.1038/sj.ejhg.5201543

Cited by 9 publications

(11 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We elected to use S100A9 as the representative antimicrobial peptide DAMP because of the possible involvement of S100A9 in psoriasis. Thus, S100A9 is consistently upregulated in psoriatic lesions and various mouse models of psoriasis (Gudjonsson and Elder, 2006;Schonthaler et al, 2013), and the expression of S100A9 and other S100A proteins is increased by cytokines that are associated with psoriasis (Nograles et al, 2010;Schonthaler et al, 2013;Waite and Skokos, 2012). In addition, recent studies have reported epigenetic alterations (hypomethylation) that result in enhanced S100A9 in psoriatic individuals (Roberson et al, 2012;Zhou et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

Choudhary

Uaratanawong

Patel

et al. 2019

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Psoriasis is a common skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes and inflammation. We previously showed that phosphatidylglycerol (PG) can regulate keratinocyte function and suppress skin inflammation. Based on data suggesting that PG can inhibit toll-like receptor (TLR) activation induced by microorganisms and their components, we determined whether PG can inhibit TLR activation in response to antimicrobial peptides. These peptides, which are up-regulated in psoriasis, are known to function as danger-associated molecular patterns (i.e., DAMPs) to activate TLRs and the innate immune system. Because S100A9 is elevated in psoriatic skin and in animal models of psoriasis, we selected S100A9 as a representative antimicrobial peptide DAMP. We showed that in primary keratinocytes and a macrophage cell line, PG suppressed inflammatory mediator production induced by recombinant S100A9 functioning through both TLR2 and TLR4. In addition, PG, but not phosphatidylcholine, inhibited downstream S100A9-elicited TLR2 and NF-kB activation. These results, to our knowledge previously unreported, show PG's ability to inhibit DAMP-induced TLR activation, thereby reducing inflammatory signals. In addition, topical PG ameliorated skin lesions and inflammation in a mouse model of psoriasis. Together, these results suggest the possibility of developing PG as a therapy for psoriasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

Choudhary

Uaratanawong

Patel

et al. 2019

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Finally, uninvolved skin of psoriatic patients grafted onto immunodeficient mice could initiate psoriatic lesions with the injection of autologous immune blood cells, but psoriasis is not initiated when a healthy skin graft was replaced in the xenograft. Moreover, a recently developed anti-T-cell biologic agent showed efficiency in relieving symptoms of psoriasis, although it is less effective than those targeting TNF-α (Gudjonsson and Elder, 2006;Sabat et al , 2007). …”

Section: Deletion Of T Cells Delays But Cannot Prevent Tgfβ1-induced mentioning

confidence: 99%

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

Han

Williams

Salter

et al. 2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Dysregulation of transformation growth factor β (TGFβ) signaling has been reported in human psoriasis. However, the causal role of TGFβ in psoriasis has not been given attention until our recent report that the transgenic mice expressing wild-type TGFβ1 in the epidermis using a keratin 5 promoter (K5.TGFβ1wt) developed psoriasis-like skin inflammation. Additional experimental data further support the causal role of TGFβ1 overexpression in psoriasis. First, we temporally induced TGFβ1 expression in keratinocytes in our gene-switch-TGFβ1wt transgenic mice and found that inflammation severity correlated with on-and-off switch of TGFβ1wt transgene expression. Second, deletion of T cells in K5.TGFβ1wt mice significantly delayed the development of psoriatic lesions. Third, therapeutic approaches effective for human psoriasis, i.e. Enbrel and Rosiglitazone (Avandia®), are also effective in relieving the symptoms seen in K5.TGFβ1wt mice. Future studies will dissect specific mechanisms and identify key factors in the TGFβ1-induced skin inflammation. Our mouse models will provide a useful tool to test novel therapeutic interventions and help to design specific therapeutic approaches for inflammatory skin disorders, including human psoriasis.

show abstract

“…This underlines the importance of other genes which may influence the genetic predisposition to the development of psoriasis. For example, additional susceptibility loci have been identified by linkage studies, highlighting several biologically relevant candidate genes of minor biological importance …”

Section: Introductionmentioning

confidence: 99%

“…For example, additional susceptibility loci have been identified by linkage studies, highlighting several biologically relevant candidate genes of minor biological importance. 1,11 Numerous genome-wide association studies (GWAS) have also been reported. In addition to strong signals in the HLA-Cw6 region, significant associations were found for genes involved in the IL-12/IL-23 ligand-receptor complex, TNF-a signalling and other cytokines, e.g.…”

Section: Introductionmentioning

confidence: 99%

TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort

Haase

Mosaad

El-Darouti

et al. 2014

Acad Dermatol Venereol

View full text Add to dashboard Cite

Replicating the association of single-nucleotide polymorphisms in the TNFAIP3, IL12B and IL23R genes with psoriasis vulgaris, in subjects from different ethnic backgrounds, underlines their importance in the pathogenesis of the disease. In contrast, the lack of any association between rs20541 (IL13) and psoriasis in our Egyptian cohort suggests the existence of important inter-ethnic genetic differences in psoriasis susceptibility.

show abstract

Mouse models: Psoriasis: an epidermal disease after all?

Cited by 9 publications

References 19 publications

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

Phosphatidylglycerol Inhibits Toll-Like Receptor–Mediated Inflammation by Danger-Associated Molecular Patterns

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort

Contact Info

Product

Resources

About