&lt;p&gt;Targeting IL-4 for the Treatment of Atopic Dermatitis&lt;/p&gt;

Chiricozzi, Andrea; Maurelli, Martina; Peris, Ketty; Girolomoni, Giampiero

doi:10.2147/itt.s260370

Cited by 67 publications

(50 citation statements)

References 67 publications

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“…Type 2 inflammation in AD is characterized by the activation of Th2 cells, T-cytotoxic 2 cells, innate lymphoid cells 2, eosinophils and mast cells, while other immune pathways such as Th22, Th17, Th9, and Th1 might contribute to maintain the pathogenic mechanism [ 71 ]. Multiple type 2 cytokines, including IL-4, IL-5, IL-9, IL-13, IL-25, IL-31, IL-33, and TSLP are overexpressed in skin and in the peripheral blood [ 72 ]. Interestingly, progression to the chronic phase of AD, which is characterized by CP and lichenification/tissue remodeling, is followed by an increased Th2-immune signature, with over-expression of pruritogenic cytokines (IL-13, TSLP) among others [ 73 ].…”

Section: The Top Itchy Skin Diseasesmentioning

confidence: 99%

Pruritus as a Distinctive Feature of Type 2 Inflammation

et al. 2021

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Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

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Section: The Top Itchy Skin Diseasesmentioning

confidence: 99%

Pruritus as a Distinctive Feature of Type 2 Inflammation

et al. 2021

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“…In the present study, the efficacy of LE extract against AD was investigated using an in vivo animal model, focusing on whether LE could improve AD-related clinical symptoms, Th1/Th2 immune balance, and restoration of skin barrier function. IgE secretion is increased in B cells by the Th2-mediated cytokine IL-4 [ 57 ], and the degranulation of mast cells by IgE increases itching through the release of histamine [ 27 , 58 ]. Continuous scratching can increase erythema, abrasions, and erosions, along with lichenification, which thickens the skin [ 59 , 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

Lee

Choung

2021

Nutrients

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The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.

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“…Thus, the reductive effect of OCL on the number of IL-4 producing cells was definitely much more pronounced for Tc2 than for Th2 T cells. Considering the pathogenic role of IL-4 in AD (and in other allergic dermatitis), IL-4 signaling is regarded as a promising potential therapeutic target for the treatment of AD [ 34 ]. Although CD4 + T cells, including naïve and Th2 cells, are regarded as the crucial source of IL-4 during Th2 responses, CD8 + T cells can also contribute to the overproduction of IL-4 in AD.…”

Section: Discussionmentioning

confidence: 99%

Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4+ and CD8+ T Cells and Counteracts the Induction of Type 1 Regulatory T Cells

Jasiecka-Mikołajczyk¹,

Jaroszewski²,

Maślanka³

2021

Molecules

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The purpose of the present study was to broaden the knowledge and understanding of the effects of oclacitinib (OCL), a Janus kinase inhibitor, on T cells in the context of both the immune mechanisms underlying anti-inflammatory and anti-allergic properties of the drug and its safety. The results indicate that beneficial effects of OCL in the treatment of skin allergic diseases may be partially mediated by the inhibition of IL-4 production in CD4+ and CD8+ T cells. To a certain extent, the antiproliferative effect of OCL on CD8+ T cells may also contribute to its therapeutic effect. The study found that OCL does not affect the proliferation of CD4+ T cells or the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells. Moreover, OCL was found to counteract the induction of type 1 regulatory T (Tr1) cells and to act as a strong inhibitor of IL-10 production in both CD4+ and CD8+ T cells. Thus, these results indicate that beneficial effects of OCL in the treatment of skin allergic diseases are not mediated through: (a) the abolishment of IFN-γ and IL-17-production in CD4+ and CD8+ T cells; (b) generation of Tr1 cells; (c) inhibition of CD4+ T cell proliferation; (d) induction of IL-10 production in CD4+ T cells. The results of this study strongly suggest that, with respect to the evaluated parameters, OCL exerts a suppressive effect on Th2- but not Th1-mediated immunity.

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<p>Targeting IL-4 for the Treatment of Atopic Dermatitis</p>

Cited by 67 publications

References 67 publications

Pruritus as a Distinctive Feature of Type 2 Inflammation

Pruritus as a Distinctive Feature of Type 2 Inflammation

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4+ and CD8+ T Cells and Counteracts the Induction of Type 1 Regulatory T Cells

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