Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, inflammation, and aberrant differentiation. Imiquimod-induced psoriasis in rodent models has been widely used to study the pathogenesis of the disease and evaluate potential therapeutic interventions. In this study, we investigated the efficacy of two commonly used treatments, Clobetasol and Tacrolimus, in ameliorating psoriatic symptoms in an Imiquimod-induced psoriasis Wistar rat model. Interestingly, rat models are poorly evaluated in the literature despite rats displaying several advantages in evaluating pharmacological substances. Psoriasis-like skin lesions were induced by topical application of Imiquimod cream on shaved dorsal skin for seven consecutive days. Following induction, rats in the treatment groups received either a Clobetasol or Tacrolimus ointment once daily for one week, while the control group did not receive any application. Disease severity was assessed using clinical scoring, histological examination, and measurement of proinflammatory cytokine levels. Both Clobetasol and Tacrolimus treatments significantly reduced psoriatic lesion severity compared to the control group. Clinical scoring revealed a decrease in erythema, scaling, transepidermal water loss, and thickness of skin lesions in both treatment groups with a more marked effect with Clobetasol. Histological analysis demonstrated reduced epidermal hyperplasia in treated animals compared to controls. Furthermore, Clobetasol led to a significant reduction in the expression levels of the interleukin-17 (IL-17a and IL-17f) proinflammatory cytokines in lesioned skin. Overall, our findings demonstrated the therapeutic efficacy of both Clobetasol and, in a modest manner, Tacrolimus in attenuating Imiquimod-induced psoriasis-like symptoms in a rat model. These results support the clinical use of these agents in the management of psoriasis and mitigating psoriatic inflammation. They also provide insights into the use of rats as a relevant species for the Imiquimod-induced psoriasis model.

Innate lymphoid cells (ILCs) are gatekeepers in barrier organs, where they maintain tissue integrity and contribute to host defense as well as tissue repair. Inappropriate activation of ILCs, however, can lead to immunopathology with detrimental results. In this study, we focused on type 1 ILCs (ILC1s), which under inflammatory conditions constitute a poorly defined population with ambiguous functions. To delineate the properties of ILC1s in skin pathology, we used the well-established mouse model of imiquimod-induced psoriasis. Although ILC1s represented a minority among cutaneous lymphocytes in vehicle-treated controls, they rapidly expanded during early psoriasis and ultimately increased by >20-fold. This rapid increase was verified using two additional psoriasis models. Inflammatory ILC1s from imiquimod-treated skin were defined as CD44+, CXCR6+, and CD11b+ and substantially contributed to TNF-α and GM-CSF production, rendering them a potential candidate to shape the inflammatory infiltrate. In accordance with the psoriasis-specific microenvironment, skin ILC1s upregulated the IL-23 receptor whereas expression of the IL-12Rβ2 subunit was diminished. As a consequence, neutralization of IL-12 only had a minor impact, whereas blocking IL-23 reduced both ILC1 abundance and disease severity. Together, our findings identify skin ILC1s as a likely player in early psoriasis and a prospective target for therapeutic approaches.

Allergic contact dermatitis (ACD) is a type IV hypersensitivity mainly mediated by Th1/Th17 immune response. Topical corticosteroid is currently the first-line treatment for allergic contact dermatitis (ACD) and systemic administration of immunosuppressive drugs are used in patients with severe disseminated cases. However, increased risk of adverse effects has limited their use. Thus, the development of a novel immunosuppressant for ACD with low toxicity is a challenging issue. In this study, we began our study by using a murine contact hypersensitivity (CHS) model of ACD to examine the immunosuppressive effects of DYRK1B inhibition. We found that mice treated with a selective DYRK1B inhibitor show reduced ear inflammation. In addition, a significant reduction of Th1 and Th17 cells in the regional lymph node upon DYRK1B inhibition was observed by FACS analysis. Studies in vitro further revealed that DYRK1B inhibitor does not only suppressed Th1 and Th17 differentiation, but also promotes regulatory T cells (Treg) differentiation. Mechanistically, FOXO1 signaling was enhanced due to the suppression of FOXO1Ser329 phosphorylation in the presence of DYRK1B inhibitor. Therefore, these findings suggest that DYRK1B regulates CD4 T cell differentiation through FOXO1 phosphorylation and DYRK1B inhibitor has a potential as a novel agent for treatment of ACD.

To evaluate the efficacy and mechanistic bases of the intravenous injection of arsenic trioxide at clinical-relevant doses for treating an imiquimod-induced psoriasis-like mouse model.

After inducing psoriasis-like skin lesions on the back of mice with imiquimod, mice in each group were injected with a clinical dose of arsenic trioxide through the tail vein. The changes in the gene expression, protein expression and distribution of relevant inflammatory factors were evaluated in the inflicted skin area, for mechanisms underlying the efficacy of intravenous As₂O₃ intervention. HaCaT cells were used to establish an in vitro psoriasis model and pcDNA3.1-NF-κB overexpression plasmid was transfected into cells to overexpress P65, which further confirmed the role of the NF-κB signaling pathway in the effectiveness of As₂O₃.

Clinical dose of As₂O₃ can significantly improve abnormal symptoms and pathological changes in psoriasis-like skin lesions induced by IMQ in mice. While IMQ induced abnormal expression and distribution of inflammatory factors in the RIG-I pathway and the microRNA-31 (miR-31) pathway in psoriatic skin tissues, intravenous As₂O₃ can effectively regulate and restore the normality. The leading role of NF-κB signaling was evidenced in vivo and validated in vitro using the NF-κB-overexpressed HaCaT cell model.

Clinical dosage of As₂O₃ may achieve effective treatment of IMQ-induced psoriatic skin lesions by modulating the NF-κB signaling pathway which regulates both the RIG-I and the miR-31 lines of action. Our data provided strong evidence supporting the claim that systemic As₂O₃ administration of clinical doses can be a promising treatment for psoriasis patients.

Allergic contact dermatitis to ion nickel (Ni+2) is an inflammatory dermatosis, common in industrialized countries. It involves the activation of nickel-specific T-cells, followed by proliferation and induction of a mixed profile of both proinflammatory and regulatory cytokines, suggesting that several T-cell subtypes (helper - Th and cytotoxic - Tc) are involved. A broader understanding of the cytokine profile may lead to new therapeutic approaches.

This study aimed to analyze the cytokines TNF-α, INF-γ, IL-2, IL-4, IL-10, IL-13, IL-17 and IL-23 using the immunohistochemistry technique in order to try to identify their prevalence in chronic and acute eczema of patients with allergic contact dermatitis to Ni+2.

We performed an immunohistochemical study for eight cytokines in 20 patients with Ni+2 allergic contact dermatitis, biopsied at the site of chronic eczema, triggered by the patient's daily contact with Ni+2, and at the site of acute eczema caused by nickel sulfate, 48 hours after applying the contact test.

The stained samples showed positive results for the eight cytokines studied. TNF-α, IFN-γ, IL-4, IL-13 and IL-17 had a higher prevalence in chronic eczema, IL-2 and IL-23 in acute eczema, and IL-10 presented a similar prevalence in both acute and chronic eczema. However, these prevalences were statistically significant only for IL-4 and IL-13.

Small sample size.

In chronic and acute eczema, we observed the presence of a mixed cytokine profile of the T cell subtypes (Th/Tc), suggesting that the responses are expressed at the same time.

This study was designed to evaluate the protective effect of ethanol extract (SEL001) isolated from a potent probiotic strain Lactobacillus sakei proBio-65 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model. Histopathological and histomorphometrical changes in the ear and dorsal skin tissues were observed under hematoxylin and eosin stain for general histopathological architectures or Masson's trichrome stain for collagen fibers. The expression profile of psoriasis-associated specific genes was determined using Real-Time PCR analysis. As a result, topical application of IMQ resulted in a significant increase of mean total and epithelial (epidermis) thicknesses, the number of inflammatory cells infiltrated in the dermis, and the decrease of dermis collagen fiber occupied regions in the ear tissues of IMQ and IMQ plus vaseline treated groups when compared to the intact control group. A significant increase of epithelial thickness and number of inflammatory cells infiltrated in the dermis of dorsal skin tissues were also noticed in IMQ and IMQ plus vaseline treated groups as compared to the intact control group, suggesting classic IMQ-induced hypersensitive psoriasis. IMQ-induced hypersensitive psoriasis related histopathological changes to the ear and dorsal skin tissues were significantly inhibited by the treatment of a standard drug clobetasol and SEL001. Further, mRNA expression analysis indicated a significant increase in gene expression levels of pro-inflammatory cytokines, including IL-19, IL-17A, and IL-23 in IMQ and IMQ plus vaseline treated groups than that of the control. Clobetasol and SEL001 treated groups resulted in a lower gene expression level of IL-19, IL-17A, and IL-23 as compared to IMQ and IMQ plus vaseline treated groups. These results enforce that SEL001 could be a novel treatment for psoriasis and an alternative to other drugs that pose a number of side effects on the skin.