Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations

Brunner, Patrick M.; Israel, Ariel; Zhang, Ning; Leonard, Alexandra; Wen, Huei‐Chi; Huynh, Thy; Tran, Gary; Lyon, Sarah; Rodriguez, Giselle; Immaneni, Supriya; Wagner, Annette; Zheng, Xiuzhong; Estrada, Yeriel; Xu, Hui; Krueger, James G.; Paller, Amy S.; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2018.02.040

Cited by 210 publications

(274 citation statements)

References 99 publications

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“…In this study, we elucidated the molecular and cellular characteristics of DN, along with its relationship with respect to CMN and MM, using a rigorous statistical method that has previously been successfully applied to the study of many cutaneous diseases, including psoriasis, alopecia areata, atopic dermatitis and skin cancers . Studies investigating the molecular profiles of melanocytic lesions that include DN are limited.…”

Section: Discussionmentioning

confidence: 99%

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Yan

Garcet

Gulati

et al. 2018

Experimental Dermatology

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Dysplastic nevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic nevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5 fold change and false discovery rate ≤ 0.05, we found differential expression of 7,186 probes (6,370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T-helper type 1 (Th1) inducing gene (IL-12), RT-PCR indicated impaired Th1 or cytotoxic T-cell response (decreased IFN-γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T-cells, exhausted T-cells, and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signaling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggest that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Yan

Garcet

Gulati

et al. 2018

Experimental Dermatology

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“…Acute AD lesions are characterized by the enhanced expression of Th2 (interleukin [IL]‐4, IL‐13, IL‐31)/Th22 (IL‐22) cytokines, while progression to chronic AD is associated with intensification of Th2/Th22 and significant increases in Th1‐related products like interferon (IFN)‐γ, C‐X‐C motif chemokine (CXCL)9 and CXCL10 . Especially, lesions of adult patients with long‐standing AD reveal extremely enhanced expression of Th1‐associated mediators (CXCL9, CXCL10, signal transducer and activator of transcription 1, IL‐12RB2), which is not seen in the lesions of pediatric AD patients with early onset . The enhanced Th1 activity may be related to the decreased expression of epidermal differentiation complex like filaggrin, and of ceramides with long‐chain fatty acids in the stratum corneum in chronic adult AD lesions .…”

Section: Discussionmentioning

confidence: 99%

Dietary habits in adult Japanese patients with atopic dermatitis

Ito

Morita

Okazaki

et al. 2019

The Journal of Dermatology

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Dietary habits can modulate the pathogenesis of atopic dermatitis. We evaluated these habits in adult Japanese patients with atopic dermatitis using a validated, brief‐type self‐administered diet history questionnaire and compared the results to those of age‐ and sex‐matched healthy controls. Patients with atopic dermatitis showed higher intakes of carbohydrate and potatoes and lower intakes of alcohol, niacin, meat and oils/fats compared with those of the healthy controls. The results of logistic regression analysis showed that the intake of alcohol was negatively associated with atopic dermatitis (odds ratio, 0.905; 95% confidence interval, 0.832–0.983; P = 0.0181). The intakes of vitamin B6 and fruit were positively correlated with the severity scoring of atopic dermatitis. Multiple regression analysis revealed that vitamin B6 intake was a predictor of the severity scoring of atopic dermatitis (β = 26.98508709, t = 2.3995292, P = 0.01933781). The intakes of vegetable fat, n‐6 polyunsaturated fatty acid, and confections were lower in the severe atopic dermatitis group (severity scoring of atopic dermatitis, ≥33) than those in the mild group. Atopic dermatitis is negatively associated with alcohol intake, and intake of vitamin B6 is a predictor of severity scoring of atopic dermatitis. The intake of n‐6 polyunsaturated fatty acid is lower in the severe atopic dermatitis group than that in the mild group. Further study is warranted on the relationships of these results with abnormal immune responses, impaired skin barrier or pruritus in atopic dermatitis.

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“…The skin transcriptome of 19 young children (with no known FLG mutations) with early‐onset AD was compared to that of age‐matched healthy controls, as well as to adult AD patients/controls. In common for both child and adult AD patients were alterations in lipid metabolism and tight junction associated genes as well as Th2‐mediated inflammation . In addition, the pediatric patients displayed significant Th17/Th22 polarization, but neither Th1 activation nor downregulation of epidermal differentiation complex genes, which are characteristic features of adult AD.…”

Section: From Disease Understanding To Biomarkers Endotypes and Tarmentioning

confidence: 99%

“…The effect of ethnicity on AD has been shown in Asian (Japanese and Korean) patients, who in general display a more psoriasiform AD phenotype and significantly higher Th17/Th22 activation as assessed by cytokine expression (IL‐17A, IL‐19, IL‐22, S100A12), compared to European American AD patients . This can have implications for the choice of treatment, as the selective blockade of IL‐17/IL‐22 pathways could be indicated in the Asian, ‘psoriasis‐like’ immune phenotype.…”

Section: From Disease Understanding To Biomarkers Endotypes and Tarmentioning

confidence: 99%

Personalized medicine—concepts, technologies, and applications in inflammatory skin diseases

Litman

2019

APMIS

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Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations

Abstract: Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.

Cited by 210 publications

References 99 publications

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Dietary habits in adult Japanese patients with atopic dermatitis

Personalized medicine—concepts, technologies, and applications in inflammatory skin diseases

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