Type 2 Inflammation Contributes to Skin Barrier Dysfunction in Atopic Dermatitis

Beck, Lisa A.; Cork, Michael J.; Amagai, Masayuki; Benedetto, Anna De; Kabashima, Kenji; Hamilton, Jennifer D.; Rossi, Ana B.

doi:10.1016/j.xjidi.2022.100131

Cited by 121 publications

(110 citation statements)

References 348 publications

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“…Since Th2 cytokine-driven inflammation and induction of impaired barriers play key roles in AD ( 36 ), the Th2 cytokines IL-4 and IL-13 were employed in various human skin models to mimic an AD-like-Th2-driven inflammatory response ( 37 – 39 ). We dissected the parameters that contribute to HSV-1 invasion in AD skin by treating human skin from healthy donors with IL-4/IL-13 to explore whether IL-induced modifications of the epidermal phenotype can per se facilitate viral penetration.…”

Section: Resultsmentioning

confidence: 99%

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients

Möckel

Cruz

Rübsam

et al. 2022

J Virol

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Section: Resultsmentioning

confidence: 99%

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients

Möckel

Cruz

Rübsam

et al. 2022

J Virol

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“…The lower incidence of non-herpetic skin infections in dupilumabtreated versus placebo-treated patients was similar to the findings in the adult dupilumab-treated population. 13 This decrease in skin infections is likely the result of improved skin barrier function, as dupilumab inhibits the type 2 cytokines that contribute to the dysregulation of protein and lipid structural and functional components of the epidermis, 19 and it also blocks antimicrobial peptide synthesis, thereby decreasing…”

Section: Ta B L Ementioning

confidence: 99%

Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

Paller

Beck

Blauvelt

et al. 2022

Pediatric Dermatology

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Background/Objective Patients with moderate‐to‐severe atopic dermatitis (AD) have increased risk of cutaneous and extracutaneous infections. Dupilumab has previously been associated with reduced risk of serious/severe infections and non‐herpetic skin infections in adults with moderate‐to‐severe AD. This analysis assessed infection rates with dupilumab versus placebo in pediatric patients with moderate‐to‐severe and severe AD participating in clinical trials. Methods This is a pooled analysis from two 16‐week, randomized, placebo‐controlled, phase 3 clinical trials of dupilumab: monotherapy in adolescents aged 12–17 years with moderate‐to‐severe AD (LIBERTY AD ADOL, NCT03054428) and with concomitant topical corticosteroids in children aged 6–11 years with severe AD (LIBERTY AD PEDS, NCT03345914). Data were pooled according to treatment received: placebo/approved dupilumab doses/other studied dupilumab doses/all dupilumab doses. Exposure‐adjusted rates (patients with ≥1 event per 100 patient‐years [nP/100 PY]) were used to compare treatment groups. Results Overall, 612 patients were included: 205 received placebo and 407 received dupilumab (261 received approved dupilumab doses and 146 received other studied dupilumab doses). Overall infection rates were numerically lower with dupilumab versus placebo (nP/100 PY: placebo, 227; approved dupilumab, 173; other dupilumab, 206; all dupilumab, 184). Total skin infections were numerically less frequent in all dupilumab‐treated groups versus placebo (nP/100 PY: placebo, 67; approved dupilumab, 30; other dupilumab, 46; all dupilumab, 36). Conclusions These data suggest that dupilumab treatment in children and adolescents with AD does not increase infection risk overall and is associated with lower rates of skin infections compared with placebo.

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“…The imbalance in T helper (Th)-2 cells is an important immunopathological characteristics of AD. JAK-STAT pathway will activated be when the cytokine binds to their specific receptor, and then start the phosphorylation cascade on the cell cytoplasmic side, leading to the transcription of the target genes [ 26 , 27 , 28 ]. Compound 1 showed a strong regulatory effect on the activity of the JAK2/STAT3 signaling pathway and may be a good promising candidate for the treatment of AD.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes

Dong

Cao

Liu

et al. 2022

IJMS

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Atopic dermatitis (AD) is a chronic inflammatory skin disease with a profound negative impact on patients’ quality of life. Four known secondary fungal metabolites were found in the chemical study of the Antarctic fungus Pleosporales sp. SF-7343, including 14-methoxyalternate C (1), 5′-methoxy-6-methyl-biphenyl-3,4,3′-triol (2), 3,8,10-trihydroxy-4-methoxy-6-methylbenzocoumarin (3), and alternariol monomethyl ether (4). Additionally, we identified the skin anti-inflammatory composition from the SF-7343 strain. Interleukin-8 and -6 Screening results showed that compound 1 inhibited IL-8 and IL-6 in tumor necrosis factor-α/interferon-γ stimulated HaCaT cells. Compound 1 showed inhibitory effects on MDC and RANTES. It also downregulated the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulated the expression of involucrin. The results of the mechanistic study showed that compound 1 inhibited the nuclear translocation of nuclear factor-kappa B p65 and STAT3. In conclusion, this study demonstrates the potential of the Antarctic fungal strain SF-7343 as a bioactive resource to inhibit skin inflammation, such as AD.

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Type 2 Inflammation Contributes to Skin Barrier Dysfunction in Atopic Dermatitis

Cited by 121 publications

References 348 publications

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients

Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data

Anti-Inflammatory Effects Exerted by 14-Methoxyalternate C from Antarctic Fungal Strain Pleosporales sp. SF-7343 via the Regulation of NF-κB and JAK2/STAT3 in HaCaT Human Keratinocytes

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