Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Czarnowicki, Tali; He, Helen; Canter, Talia; Han, Joseph; Lefferdink, Rachel; Erickson, Taylor; Rangel, Stephanie M.; Kameyama, Naoya; Kim, Hyun Je; Pavel, Ana B.; Estrada, Yeriel; Krueger, James G.; Paller, Amy S.; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2019.09.031

Cited by 88 publications

(94 citation statements)

References 87 publications

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“…Studies have revealed that the Th1, Th2, Th22, and Th17 cells are involved in the pathogenesis of AD ( Figure 2) (135,136). It has been demonstrated that Th22 and Th17 immune responses contribute to chronic skin lesions of AD, especially in pediatric, intrinsic, and Asian patients (137)(138)(139)(140).…”

Section: Atopic Dermatitismentioning

confidence: 99%

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

et al. 2020

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Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4 + helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

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Section: Atopic Dermatitismentioning

confidence: 99%

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

et al. 2020

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“…This also renders a disfavour to an increasingly embraced personalized medicine and pheno-and endotype-based approach to AD therapy. 77 Thus, we propose that the distinction between defined AD phenotypes and endotypes 9,10,78 should already begin at the level of preclinical animal research. 79…”

Section: Whi Ch Ad Phenot Ype and Endot Ype Is B Eing Modelled?mentioning

confidence: 99%

Mouse models of atopic dermatitis: a critical reappraisal

Gilhar

Reich

Keren

et al. 2021

Experimental Dermatology

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Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research. Here, we propose to initiate a rational debate on the minimal criteria that a mouse model should meet in order to be considered relevant for human AD. We

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“…While in adults, whole‐skin tissues have been instrumental in identifying biomarkers to track cutaneous disease severity and therapeutic response, 6‐11 biopsies are largely not feasible in children. Furthermore, studies in blood are not able to capture the distinct immune and barrier profiles of lesional and non‐lesional AD skin 12‐14 …”

Section: Introductionmentioning

confidence: 99%

Tape strips from early‐onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin

Pavel

Renert‐Yuval

et al. 2020

Allergy

Self Cite

108

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Background: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early-onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent-onset, moderate-to-severe AD using tape strips. Methods: Sixteen tape strips were collected for RNA-seq profiling from 19 infants/ toddlers (<5 years old; lesional and nonlesional) with early-onset moderate-to-severe AD (≤6 months) and 17 healthy controls. Results: We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold-change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)-related genes, largely lacking significant Th1-skewing. Significant down-regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene-subsets and individual genes (FLG with IL-4R and CCL17; r < −0.4, P < .05).

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Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Cited by 88 publications

References 87 publications

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

Mouse models of atopic dermatitis: a critical reappraisal

Tape strips from early‐onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin

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