RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications

Suárez‐Fariñas, Mayte; Ungar, Benjamin; Rosa, Joel Correa da; Ewald, David Adrian; Rozenblit, Mariya; Gonzalez, Juana; Xu, Hui; Zheng, Xiuzhong; Peng, Xiangyu; Estrada, Yeriel; Dillon, Stacey R.; Krueger, James G.; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2015.03.003

Cited by 231 publications

(210 citation statements)

References 51 publications

(67 reference statements)

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…10,23,25,33,34,43 To assess distinct features of the Asian AD phenotype, we conducted the first head-to-head comparison between Asian patients with AD and EA patients with AD using psoriasis as a point of reference and using skin samples obtained from each racial group.…”

Section: Discussionmentioning

confidence: 99%

“…Not only are expression patterns different when comparing respective lesional and nonlesional skin of Asian and EA patients with AD, but also significant differences were detected when comparing relative lesional versus nonlesional expression (previously defined as disease phenotype) 10,33,34 between AD groups and patients with psoriasis. Fig 5 illustrates a heat map showing expression differences (in FCHs) between lesional versus nonlesional skin of Asian and EA patients with extrinsic AD, as well as patients with psoriasis.…”

Section: Prominent Epidermal Hyperplasia and Frequent Parakeratosis Cmentioning

confidence: 99%

See 1 more Smart Citation

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Noda

Suárez‐Fariñas

Ungar

et al. 2015

Journal of Allergy and Clinical Immunology

Self Cite

513

478

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Prominent Epidermal Hyperplasia and Frequent Parakeratosis Cmentioning

confidence: 99%

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Noda

Suárez‐Fariñas

Ungar

et al. 2015

Journal of Allergy and Clinical Immunology

Self Cite

513

478

View full text Add to dashboard Cite

“…IL-36 cytokines are overexpressed in affected skin of patients with inflammatory skin diseases, including atopic dermatitis and psoriasis (25)(26)(27)(28). The functional importance of this upregulation is supported by several recent findings: IL-36g mediates the alarmin function of the antimicrobial peptide LL37, and it functions as an alarmin that signals pathogen infections (20,29); injection of IL-36a promotes myeloid cell infiltration and their activation in the skin (30); tg mice overexpressing IL-36a in keratinocytes develop a psoriasis-like phenotype (31); the psoriasiform dermatitis that develops in mice after treatment with imiquimod depends on an IL-36-mediated cross-talk between dendritic cells and keratinocytes (32); and IL-36RA deficiency causes generalized pustular psoriasis in humans (33).…”

Section: Discussionmentioning

confidence: 99%

Autocrine and Paracrine Regulation of Keratinocyte Proliferation through a Novel Nrf2–IL-36γ Pathway

Kurinna

Muzumdar

Köhler

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

The Nrf2 transcription factor is well known for its cytoprotective functions through regulation of genes involved in the detoxification of reactive oxygen species or toxic compounds. Therefore, activation of Nrf2 is a promising strategy for the protection of tissues from various types of insults and for cancer prevention. However, recent studies revealed a proinflammatory activity of activated Nrf2 and a stimulating effect on epithelial cell proliferation, but the underlying mechanisms of action and the responsible target genes are largely unknown. Using a combination of gene expression profiling, chromatin immunoprecipitation, and targeted proteomics via selected reaction monitoring, we show that the gene encoding the proinflammatory cytokine IL-36γ is a novel direct target of Nrf2 in keratinocytes and hepatocytes in vitro and in vivo. As a consequence, upregulation of IL-36γ expression occurred upon genetic or pharmacological activation of Nrf2 in the epidermis and in the normal and regenerating liver. Functional in vitro studies demonstrate that IL-36γ directly stimulates proliferation of keratinocytes. In particular, it induces expression of keratinocyte mitogens in fibroblasts, suggesting that the Nrf2–IL-36γ axis promotes keratinocyte proliferation through a double paracrine loop. These results provide mechanistic insight into Nrf2 action in the control of inflammation and cell proliferation through regulation of a proinflammatory cytokine with a key function in various inflammatory diseases.

show abstract

“…Subsequent studies found that IL-36 isoforms are highly expressed in human skin in pustular psoriasis and other forms of psoriasis (Johnston et al, 2016). Recently, the IL-36 isoforms, IL-36α and IL-36γ , were also found to be expressed in human AD skin (Suarez-Farinas et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses

Liu

Archer

Dillen

et al. 2017

Cell Host & Microbe

195

168

View full text Add to dashboard Cite

SUMMARY Staphylococcus aureus colonization contributes to skin inflammation in diseases such as atopic dermatitis, but the signaling pathways involved are unclear. Herein, epicutaneous S. aureus exposure to mouse skin promoted MyD88-dependent skin inflammation initiated by IL-36 but not IL-1α/β, IL-18 or IL-33. By contrast, an intradermal S. aureus challenge promoted MyD88-dependent host defense initiated by IL-1β rather than IL-36, suggesting that different IL-1 cytokines trigger MyD88-signaling depending on the anatomical depth of S. aureus cutaneous exposure. The bacterial virulence factor PSMα but not α-toxin or δ-toxin contributed to the skin inflammation, which was driven by IL-17-producing γδ and CD4+ T cells via direct IL-36R-signaling in the T cells. Finally, adoptive transfer of IL-36R-expressing T cells to IL-36R-deficient mice was sufficient for mediating S. aureus-induced skin inflammation. Together, this study defines a previously unknown pathway by which S. aureus epicutaneous exposure promotes skin inflammation involving IL-36R/MyD88-dependent IL-17 T cell responses.

show abstract

RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications

Cited by 231 publications

References 51 publications

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Autocrine and Paracrine Regulation of Keratinocyte Proliferation through a Novel Nrf2–IL-36γ Pathway

Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses

Contact Info

Product

Resources

About