Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis

Hawerkamp, Heike C.; Fahy, Caoimhe M. R.; Fallon, Padraic G.; Schwartz, Christian

doi:10.1002/ski2.99

Cited by 6 publications

(4 citation statements)

References 222 publications

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“…The capacity of the structural keratinocytes to produce a diversity of cytokines and chemokines, along with the hyperproliferation process, lead to a vicious pathogenesis cycle. Proinflammatory Th 1 and Th 17 cells dominate the affected skin, producing changes in the microbiome composition and production of antimicrobial peptides [9]. Some genes involved in the skin barrier function are linked to psoriasis.…”

Section: Psoriasis and Allergic Contact Hypersensitivity As T-cell-me...mentioning

confidence: 99%

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview

et al. 2022

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The dysfunctionality of the protective skin barrier in psoriasis allows easier cutaneous penetration of various contact haptens; thus, such patients can develop allergic contact hypersensitivity as a comorbidity. Both skin conditions involve T-cell-mediated mechanisms. Dermatologists and allergists should consider assessing allergic contact cell-mediated hypersensitivity in selected psoriasis patients, especially those with palmoplantar psoriasis and who are refractory to topical treatments, and in patients with psoriasis, with or without arthritis, treated with biologics that present skin lesions clinically suggestive of contact dermatitis.

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Section: Psoriasis and Allergic Contact Hypersensitivity As T-cell-me...mentioning

confidence: 99%

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview

et al. 2022

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“…Although the importance of epidermal barrier in AD pathogenesis has been well-recognized, little is known about mechanistically how barrier dysregulation facilitates disease progression especially at the epidermal-innate immune interface ( 14, 53 ). To seek insights into the skin immunological responses to Ovol1 deletion-instigated, AD-associated epidermal dysregulation, we used flow cytometry to compare the immune cell profiles in control and SSKO skin during homeostasis and AD-like inflammation.…”

Section: Resultsmentioning

confidence: 99%

An AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes skin homeostasis against atopic dermatitis

Chen,

Dragan,

Sun

et al. 2024

Preprint

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Skin is our outer permeability and immune defense barrier against myriad external assaults. Aryl hydrocarbon receptor (AhR) senses environmental factors and regulates barrier robustness and immune homeostasis. AhR agonist is in clinical trial for atopic dermatitis (AD) treatment, but the underlying mechanism of action remains ill-defined. Here we reportOVOL1/Ovol1as a conserved and direct transcriptional target of AhR in epidermal keratinocytes. We show that OVOL1/Ovol1 impacts AhR regulation of keratinocyte gene expression, andOvol1deletion in keratinocytes hampers AhR’s barrier promotion function and worsens AD-like inflammation. Mechanistically, we identify Ovol1’s direct downstream targets genome-wide, and providein vivoevidence for Id1’s critical role in barrier maintenance and disease suppression. Furthermore, our findings reveal an IL-1/dermal γδT cell axis exacerbating both type 2 and type 3 immune responses downstream of barrier perturbation inOvol1-deficient AD skin. Finally, we present data suggesting the clinical relevance of OVOL1 and ID1 function in human AD. Our study highlights a keratinocyte-intrinsic AhR-Ovol1-Id1 regulatory axis that promotes both epidermal and immune homeostasis against AD-like inflammation, implicating new therapeutic targets for AD.

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“…The two most important chronic diseases of the skin are atopic dermatitis (AD) and psoriasis, both of which have been associated with obesity. While AD is classically regarded as a Th2-biased chronic allergic inflammatory skin disease with contribution of eosinophils, basophils, mast cells and ILC2 to pathogenicity, psoriasis is driven by a Th1/Th17-biased immune response and includes neutrophils and ILC3 (172). Both AD and psoriasis have been associated with obesity (reviewed in (173)(174)(175)(176)).…”

Section: Skin Inflammationmentioning

confidence: 99%

“…An important factor promoting the development of AD is the breakdown of the skin barrier ( 172 , 183 ), which can be measured by trans-epidermal water loss (TEWL). Importantly, TEWL is significantly increased in people with obesity ( 184 , 185 ).…”

Section: Th2 Cell Function During Obesity and Malnutritionmentioning

confidence: 99%

Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back

et al. 2022

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Over the past decades, the relationship between the immune system and metabolism has become a major research focus. In this arena of immunometabolism the capacity of adipose tissue to secrete immunomodulatory molecules, including adipokines, within the underlying low-grade inflammation during obesity brought attention to the impact obesity has on the immune system. Adipokines, such as leptin and adiponectin, influence T cell differentiation into different T helper subsets and their activation during immune responses. Furthermore, within the cellular milieu of adipose tissue nutrient availability regulates differentiation and activation of T cells and changes in cellular metabolic pathways. Upon activation, T cells shift from oxidative phosphorylation to oxidative glycolysis, while the differential signaling of the kinase mammalian target of rapamycin (mTOR) and the nuclear receptor PPARγ, amongst others, drive the subsequent T cell differentiation. While the mechanisms leading to a shift from the typical type 2-dominated milieu in lean people to a Th1-biased pro-inflammatory environment during obesity are the subject of extensive research, insights on its impact on peripheral Th2-dominated immune responses become more evident. In this review, we will summarize recent findings of how Th2 cells are metabolically regulated during obesity and malnutrition, and how these states affect local and systemic Th2-biased immune responses.

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Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis

Cited by 6 publications

References 222 publications

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview

An AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes skin homeostasis against atopic dermatitis

Obesity-Mediated Immune Modulation: One Step Forward, (Th)2 Steps Back

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