TSLP and IL-7R Variants Are Associated with Persistent Atopic Dermatitis

Berna, Ronald; Mitra, Nandita; C, Lou; Wan, Joy; Hoffstad, Ole; Wubbenhorst, Bradley; Nathanson, Katherine L.; Margolis, David J.

doi:10.1016/j.jid.2020.05.119

Cited by 23 publications

(17 citation statements)

References 19 publications

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“…A cohort study following more than 800 American children showed that the TSLPrs1898671 homozygosity contributed to the less-persistent AD in White children ( 53 ). More recently, another large-scale longitudinal cohort study found that the IL-7R variant rs11567725 can regulate the function of TSLP variants, suggestive of TSLP to be a potential genetic risk evaluation index of AD ( 54 ). These findings revealed that the epidermal production of TSLP is correlated with the clinically observed lesions, severity, and persistence of AD.…”

Section: Tslp and Cutaneous Immune-mediated Disordersmentioning

confidence: 99%

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

Wang

Zuo

2021

Front. Immunol.

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Thymic stromal lymphopoietin (TSLP) was initially demonstrated to be critical in regulating inflammatory responses among various allergic disorders (such as atopic dermatitis, food allergy, and asthma). Although two isoforms (short form and long form) of TSLP have been demonstrated in human tissues, the long form of TSLP (lfTSLP) is strongly implicated in the pathogenesis of allergies and cutaneous immune-mediated diseases. The immunomodulatory activity of lfTSLP varies widely, driving T helper (Th) cells polarizing Th2 and Th17 immune responses and inducing itch. Moreover, lfTSLP is closely associated with skin fibrosis, epidermal hyperplasia, angiogenesis, and homeostatic tolerogenic regulations. This review highlights significant progress from experimental and clinical studies on lfTSLP in cutaneous immune-mediated diseases (atopic dermatitis, psoriasis, bullous pemphigoid, systemic sclerosis, chronic spontaneous urticaria, Behçet’s disease, vitiligo, rosacea, systemic lupus erythematosus, and alopecia areata). We also offer original insights into the pleiotropic properties of the cytokine TSLP in various pathophysiological conditions, with significant clinical implications of TSLP-targeted therapies for immune-mediated skin diseases in the future.

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Section: Tslp and Cutaneous Immune-mediated Disordersmentioning

confidence: 99%

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

Wang

Zuo

2021

Front. Immunol.

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“…The PEER study was approved by the Institutional Review Board of the University of Pennsylvania (Philadelphia, PA), and written informed consent was obtained from all participants or from their caregivers. Both the overall PEER cohort and the subset with genetic data have been previously described ( Berna et al., 2021 ; Margolis et al., 2014c ). This study examines only individuals self-described as African American.…”

Section: Methodsmentioning

confidence: 99%

“…Other skin barrier proteins in this family include FLG-2, TCHHL1, and hornerin ( Margolis et al., 2014a ; Pellerin et al., 2013 ; Pendaries et al., 2015 ; Wu et al., 2011b ). In a previous study, we conducted next-generation sequencing of TSLP and IL7R and identified specific genetic variants likely to have a function in AD ( Berna, 2021 ). However, this study was limited by the inability to effectively examine low-frequency (1% < minor allele frequency [MAF] < 5%) and rare (MAF < 1%) variants ( Berna, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…In a previous study, we conducted next-generation sequencing of TSLP and IL7R and identified specific genetic variants likely to have a function in AD ( Berna, 2021 ). However, this study was limited by the inability to effectively examine low-frequency (1% < minor allele frequency [MAF] < 5%) and rare (MAF < 1%) variants ( Berna, 2021 ). Indeed, a key limitation of examining uncommon variants with next-generation sequencing studies is that one requires very large sample sizes to effectively examine such variants, an expensive and laborious endeavor.…”

Section: Introductionmentioning

confidence: 99%

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Using a Machine Learning Approach to Identify Low-Frequency and Rare FLG Alleles Associated with Remission of Atopic Dermatitis

et al. 2021

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“…Among the sixty-eight genes differentially methylated, key regulatory pathways concerning developmental, metabolic, and inflammatory processes were most involved [80]. Interestingly, prenatal exposure to maternal cigarette smoke has been linked to the abnormal DNA methylation status of the 5 -CpG-island in the thymic stromal lymphopoietin (TSLP [81]), a key immune cytokine gene involved in the pathogenesis of asthma [82,83], atopic dermatitis [84], and pediatric eosinophilic esophagitis [85].…”

Section: Fetal Epigenetic Changes: Studies On Cord Blood Cellsmentioning

confidence: 99%

Epigenetic Changes Induced by Maternal Factors during Fetal Life: Implication for Type 1 Diabetes

Barchetta

Arvastsson

Sarmiento

et al. 2021

Genes

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Organ-specific autoimmune diseases, such as type 1 diabetes, are believed to result from T-cell-mediated damage of the target tissue. The immune-mediated tissue injury, in turn, is known to depend on complex interactions between genetic and environmental factors. Nevertheless, the mechanisms whereby environmental factors contribute to the pathogenesis of autoimmune diseases remain elusive and represent a major untapped target to develop novel strategies for disease prevention. Given the impact of the early environment on the developing immune system, epigenetic changes induced by maternal factors during fetal life have been linked to a likelihood of developing an autoimmune disease later in life. In humans, DNA methylation is the epigenetic mechanism most extensively investigated. This review provides an overview of the critical role of DNA methylation changes induced by prenatal maternal conditions contributing to the increased risk of immune-mediated diseases on the offspring, with a particular focus on T1D. A deeper understanding of epigenetic alterations induced by environmental stressors during fetal life may be pivotal for developing targeted prevention strategies of type 1 diabetes by modifying the maternal environment.

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TSLP and IL-7R Variants Are Associated with Persistent Atopic Dermatitis

Cited by 23 publications

References 19 publications

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

Using a Machine Learning Approach to Identify Low-Frequency and Rare FLG Alleles Associated with Remission of Atopic Dermatitis

Epigenetic Changes Induced by Maternal Factors during Fetal Life: Implication for Type 1 Diabetes

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