The IL-4, IL-13 and IL-31 pathways in atopic dermatitis

Dubin, Celina; Duca, Ester Del; Guttman‐Yassky, Emma

doi:10.1080/1744666x.2021.1940962

Cited by 87 publications

(85 citation statements)

References 220 publications

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“…In the acute phase, Th2 lymphocytes mount strong inflammatory responses with the secretion of type-2 cytokines, such as IL-4 and IL-13, which downregulate the levels of FLG, loricrin (LOR), and involucrin (INV) in keratinocytes, and exacerbates epidermal barrier dysfunction [ 10 ]. Keratinocytes constitutively express functional IL-4 and IL-13 receptors [ 39 ] and produce the eosinophil chemokine CCL26 in response to IL-4 and IL-13. Other than regulating IgE antibody production in B cells, IL-4 and IL-13 have been reported to act directly on itch-sensory neurons to promote itch [ 40 , 41 ].…”

Section: Active Participation Of Inflammatory Cytokines During Ad Evo...mentioning

confidence: 99%

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

Fania

Moretta

Antonelli

et al. 2022

IJMS

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Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

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Section: Active Participation Of Inflammatory Cytokines During Ad Evo...mentioning

confidence: 99%

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

Fania

Moretta

Antonelli

et al. 2022

IJMS

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“…As a mediator for IL-4 and IL-13 acting on downstream inflammatory cells, IL-4R complex participate in multiple signaling pathways that related to AD immune dysregulation [ 42 , 43 ].Yun et al [ 44 ] reported treating 2,4-dinitrochlorobenzene (DNCB)-induced AD mice with echinochrome A (an anti-inflammatory and anti-oxidative drug), revealing that echinochrome A appeared to suppress the expression and secretion of the proinflammatory cytokine IL-4 and IL-13. A recent study showed that the clinical features of experimental atopic dermatitis are driven by IL-4 and IL-13 signaling via IL-4R and highlighted that IL-4R might serve as a potent therapeutic target for the treatment of AD and other allergic diseases [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model

Guan

et al. 2022

Stem Cell Res Ther

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Background Mesenchymal stem cells (MSCs) have therapeutic potential for atopic dermatitis (AD) owing to their immunoregulatory effects. However, the underlying mechanisms associated with the therapeutic efficacy of MSCs on AD are diverse and related to both cell type and delivery method. Objectives This study investigated the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin (OVA)-induced AD mouse model. Methods AD mice were subcutaneously injected with mouse ADSCs, cortisone, or PBS, and the therapeutic effects were determined by gross and histological examinations and serum IgE levels. Additionally, qPCR, RNA-sequencing analyses of skin samples and co-culture of ADSCs and Th17 cells were conducted to explore the underlying therapeutic mechanisms. Results ADSCs treatment attenuated the AD pathology, decreased the serum IgE levels, and decreased mast cells infiltration in the skin of the model mice. Moreover, tissue levels of IL-4R and Th17-relevant products (IL-17A, CCL20, and MMP12) were suppressed in the ADSC- and cortisone-treated groups. Genomics and bioinformatics analyses demonstrated significant enrichment of inflammation-related pathways in the downregulated genes of the ADSC- and cortisone-treated groups, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the proliferation of Th17 cells and the expression of proinflammatory cytokines (IL-17A and RORγT). Furthermore, expression levels of PD-L1, TGF-β, and PGE2 were significantly upregulated in co-cultured ADSCs relative to those in monocultured ADSCs. Conclusion ADSCs ameliorate OVA-induced AD in mice mainly by downregulating IL-17 secretion of Th17 cells.

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“…12 Thus, it is predictable that GA might also have an effect on AD immune system as previously reported. 28 However, as AD is always sustained for a long time, the safety of GA for long-term use still needs investigation, and it also needs to be used with caution if there is a constant down-modulation of the immune system resulting from the GA treatment.…”

Section: Discussionmentioning

confidence: 99%

Gallic Acid Ameliorates Atopic Dermatitis-Like Skin Inflammation Through Immune Regulation in a Mouse Model

Hu¹,

Zhou²

2021

CCID

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The IL-4, IL-13 and IL-31 pathways in atopic dermatitis

Cited by 87 publications

References 220 publications

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model

Gallic Acid Ameliorates Atopic Dermatitis-Like Skin Inflammation Through Immune Regulation in a Mouse Model

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