Imiquimod-induced Psoriasis Research Articles

Therapeutic Potential of Piper Betle Gel in the Management of Imiquimod-Induced Psoriasis: A Focus on Inflammatory Pathway Modulation

Therapeutic Potential of Piper Betle Gel in the Management of Imiquimod-Induced Psoriasis: A Focus on Inflammatory Pathway Modulation

Gypenosides alleviates HaCaT keratinocyte hyperproliferation and ameliorates imiquimod-induced psoriasis in mice.

Psoriasis is an autoimmune skin condition characterized by hyperproliferation of keratinocytes and chronic immune responses. Gypenosides (Gyp) exhibits anti-proliferative and anti-inflammatory effects on different diseases. However, its functioning and mechanism of Gyp on psoriasis remains unknown. To explore the effect and mechanism of Gyp on psoriasis. The impact and mechanism of Gyp on psoriasis in vitro and in vivo were probed through cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, reverse transcription quantitative polymerase chain reaction, hematoxylin and eosin staining, enzyme-linked immunosorbent serologic assay, immunofluorescence, and Western Blotting assays. Gyp inhibited cell proliferation and the release of inflammatory cytokinesin interleukin (IL-22)-induced spontaneously transformed human aneuploid immortal keratinocyte cell line (HaCaT). In addition, Gyp demonstrated enhancement in erythema and scaling as well as reductions in the thickness of epidermal layers, release of inflammatory factors, and Ki-67 (a nuclear protein) level in imiquimod (IMQ)-induced mice. Mechanistically, Gyp upregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) expression and diminished the level of p-p65/p65 and p-STAT3/STAT3 in skin tissues from IMQ-induced mice and IL-22-induced HaCaT cells, which were reversed with the application of ML385, an inhibitor of Nrf2. In addition, the administration of ML385 reversed decrease in cell viability and reduced the expressions of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in IL-22-induced HaCaT cells caused by Gyp. In summary, Gyp reduced excessive cell growth and inflammation in psoriasis by suppressing nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) through activation of Nrf2.

Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Phosphatidylserine Topically Attenuates Imiquimod-induced Psoriasis Through Inflammation Inhibition in Mice.

Psoriasis is a chronic skin condition that is associated with persistent inflammation and skin lesions. Topical therapy has been a promising approach to the alleviation of psoriasis through the application of anti-inflammatory agents. Phosphatidylserine (PS) administration has shown anti-inflammatory effects in the trials. Consequently, the objective of this study was to evaluate the effects of topical PS on the potential improvement of an imiquimod (IMQ)-induced psoriasis model. Additionally, cyclosporine A was utilized as a comparative anti-psoriatic agent in our study. The psoriasis model was established by topically applying IMQ to the dorsal skin of mice once daily for five consecutive days. The efficacy of topical PS was assessed using the Psoriasis Area and Severity Index (PASI) score to evaluate skin lesions. Subsequently, the skin samples were analyzed using Baker's scoring system, Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis. IMQ-induced plaque-type psoriasis resulted in a significant increase (P<0.05) in dermal thickness, hyperkeratosis, PASI score, and inflammatory cytokines at the lesion site. The topical PS and cyclosporine A significantly (P<0.05) reduced PASI score and dermal thickness, while also alleviating erythema and scaling when compared to untreated mice. Furthermore, biomolecular assessments revealed that PS significantly (P<0.05) inhibited the gene expression of IL-17, IL-23, and TNF-α cytokines in the IMQ-induced lesions. Topical PS may pointedly alleviate psoriasis through the inhibition of inflammation. The beneficial effects of the PS recommend further investigation in both experimental and clinical studies in the control of skin psoriasis.

Modulation of Plet1 expression by N-Acetylglucosamine through the IL-17A-MAPK pathway in an imiquimod-induced psoriasis mouse model.

Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17A stimulated human dermal fibroblasts (HDF), along with IL-17A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.

Skin-permeable gold nanoparticles with modifications azelamide monoethanolamine ameliorate inflammatory skin diseases

BackgroundTraditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases.MethodsHere, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs.ResultsWe found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9.ConclusionAu-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.

Development of selective heterocyclic PDE4 inhibitors for treatment of psoriasis

Psoriasis is a chronic autoimmune disease that badly affects the life quality of patients and their families. Inadequate efficacy, safety risks, high cost and low compliance of current psoriasis drugs urge development of novel small molecular drugs. In this study, two series of 37 novel compounds were designed and synthesized as inhibitors of phosphodiesterase 4 (PDE4) that specifically hydrolyzes second messenger cAMP and is an effective target for treatment of inflammatory diseases. Comprehensive structural-activity optimization led to finding of inhibitor 2e with IC50 = 2.4 nM for PDE4D and >4100-fold selectivity over other PDE families. Compound 2e inhibited the release of TNF-α (IC50 = 21.36 μM) and IL-6 (IC50 = 29.22 μM) in the LPS-stimulated Raw264.7 cells. Topical application of 2e exhibited remarkable therapeutic efficacy in imiquimod-induced psoriasis mice model, suggesting that 2e is a strong drug candidate for treatment of psoriasis.

Recombinant ISRAA ameliorates imiquimod-induced psoriasis and knocking out Israa delays its onset.

Psoriasis, an inflammatory disease, is largely mediated by T-helper 17 cytokines. We have previously identified the immune system-released activating agent (Israa) as a novel gene that connects the nervous and immune systems. This research aims to investigate the role of the Israa gene in psoriasis in vivo using the imiquimod-induced psoriasis model. We established the model in C57BL/6 wildtype mice, which were then treated with 200 pg/mouse, 400 pg/mouse, or 800 pg/mouse of recombinant ISRAA compared to methotrexate. Subsequently, we also induced psoriasis in Israa-knockout mice to confirm the effect of Israa. Results consistently showed improvement in psoriasis in all groups receiving recombinant ISRAA. The 200 pg/mouse dose eliminated the disease, reduced the cutaneous release of IL-17 to one-third and TNF-α to one-sixth, increased IL-10 release to over 500 pg, completely resolved parakeratosis, decreased epidermal thickness to one-half, and reduced the expression of CD4 and neutrophil elastase in the skin (all p < 0.05). Israa-knockout mice exhibited less severe psoriasis in all scoring, biochemical, and histological parameters compared to wild-type mice (p < 0.05). This study highlights Israa as a crucial molecule in psoriasis and confirms its immunomodulatory role in inflammatory diseases.

Attenuated Effects of Topical Empagliflozin on Imiquimod-induced Model of Psoriasis in Mice

Empagliflozin is a sodium-glucose cotransporter inhibitor (SGLT2) that drops blood glucose levels by inhibiting glucose reabsorption and encouraging glucose excretion. Other benefits of empagliflozin include cardiovascular protection, lowering uric acid levels, and reducing liver damage brought on by non-alcoholic fatty liver disease (NAFLD). to investigate the possible influence of two different concentrations of empagliflozin gel on psoriasis induced via imiquimod in mice. dividing 40 mice into five groups (8 mice for each group). All groups gated imiquimod to induce psoriasis (except group I) for seven days. The induction group (Group II) received imiquimod cream for seven days. The rest of the groups gated Clobetasol propionate cream 0.05%, empagliflozin 1% gel, and empagliflozin 3% gel, respectively, once daily for seven days after seven days of induction by imiquimod. The outcomes exhibited that topical empagliflozin had important anti-psoriatic activity by diminishing the Psoriasis Area Severity Index (PASI) score and improving histological alterations during imiquimod application; moreover, it elevated anti-inflammatory biomarker IL-37 and lowered inflammatory biomarkers TNF-α and IL-17. Empagliflozin has substantial anti-psoriatic action against imiquimod-induced psoriasis through its anti-proliferative and anti-inflammatory effects. Also, empagliflozin has a restorative effect on the histopathological alterations of mice's skin induced by imiquimod

Salidroside alleviates imiquimod-induced psoriasis by inhibiting GSDMD-driven keratinocyte pyroptosis.

Psoriasis is a common immune-related polygenic inflammatory skin disease. Salidroside (SAL) exerts anti-inflammatory and antioxidant effects and is used to treat skin diseases. However, the specific effects of SAL on psoriasis remain unclear. In this study, we aimed to investigate the efficacy of SAL for psoriasis treatment. Mice were treated with imiquimod (IMQ) to establish an in vivo psoriasis model. Histological analysis was conducted via hematoxylin and eosin staining. Cytokine release was determined via enzyme-linked immunosorbent assay. Additionally, mRNA levels were determined via reverse transcription-quantitative polymerase chain reaction. Protein expression was assessed via Western blotting. Gasdermin D (GSDMD) and Ki-67 expression levels were determined via immunohistochemistry. Caspase 1 and GSDMD expression levels were determined via immunofluorescence assay. Furthermore, macrophage function and keratinocyte pyroptosis were also analyzed via flow cytometry. Cell proliferation was determined using 5-ethynyl-2'deoxyuridine assay. SAL alleviated IMQ-induced psoriasis. IMQ-mediated GSDMD-driven pyroptosis and keratinocyte hyperproliferation promoted M1 macrophage polarization. However, SAL treatment suppressed GSDMD expression, thereby inhibiting keratinocyte proliferation and pyroptosis and promoting M2 macrophage polarization. GSDMD deficiency further promoted the effects of SAL and suppressed psoriasis progression. Overall, our findings suggest that SAL exerts protective effects against psoriasis. Specifically, it exerts anti-inflammatory effects by regulating M2 macrophage polarization and inhibiting keratinocyte pyroptosis-driven proliferation induced by the immune microenvironment in psoriasis.

Cannabidiol Alleviates Imiquimod-Induced Psoriasis by Inhibiting JAK2-STAT3 in a Mouse Model.

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1-3% of the global population; however, the mechanisms remain unclear. This study investigated CBD's effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2-STAT3 signaling pathway, leading to the downregulation of Il1b, Il6, Il12b, Il17a, Il22, and Tnf expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2-STAT3 pathway.

Alleviative effects of combined topical melatonin and rutin on imiquimod-induced psoriasis mouse model

Background: Psoriasis is a longstanding autoimmune dermatosis with thickened, reddish-brown, and flaking skin lesions. Melatonin is an indolamine hormone exhibiting antioxidant, anti-inflammatory, and anti-proliferative actions. Rutin is a nutritional flavonoid possessing antioxidative, anti-inflammatory, and immunomodulatory properties. Aim: To explore the potential anti-psoriatic activity of combined topical melatonin and rutin. Methods: 70 albino mice were divided into 7 groups of 10 each. The impacts of clinical observation, histopathological examination, and biomarker analysis were estimated. Results: Combined topical melatonin and rutin effectively diminished imiquimod-induced elevated PASI and Baker’s scores and corrected histopathological aberrations. Diminished inflammatory indicators like TNF-α and IL-17A, angiogenic elements like VEGF, oxidative elements like MDA, and proliferative elements like Ki-67 were also noted. Conclusion: Combined topical melatonin and rutin have profound anti-psoriatic effects.

Coleus forskohlii shows anti-psoriatic activity in imiquimod-induced psoriasis rats

Objective: To evaluate anti-psoriatic activity of Coleus forskohlii in rats with imiquimod-induced psoriasis. Methods: Imiquimod was used to induce psoriasis in rats. Body weight, skin thickness, erythema, scaling, spleen weight, and histological alternations were measured to assess the effect of Coleus forskohlii. Furthermore, an emulgel formulation containing Coleus forskohlii 10% was prepared and characterized along with its ex vivo permeation studies. Results: The emulgel formulation containing Coleus forskohlii 10% had a pH of 5.40±0.36, with optimum spreadability of (31.67±2.08) g/(cms) and viscosity of (15 966.67±1 274.10) cps, and enhanced both the rate and the extent of drug permeation through psoriatic skin. In an ex vivo study, the quantity of drug permeated (19.18%), deposited (52.38%), and drug remaining in the donor compartments (28.31%) was satisfactory. Coleus forskohlii significantly alleviated imiquimod-induced psoriasis by increasing glutathione and superoxide dismutase activity, decreasing malondialdehyde and nitric oxide levels, and alleviating histological alternations in rat skin. Conclusions: Coleus forskohlii can alleviate imiquimod-induced psoriasis, which may be used as a therapeutic candidate for the treatment of psoriasis.

51922 IL-17RA signaling in mesoderm-derived stromal cells promotes mouse imiquimod-induced psoriasis

51922 IL-17RA signaling in mesoderm-derived stromal cells promotes mouse imiquimod-induced psoriasis

A transdermal delivery system using microneedle patches containing poly(lactic-co-glycolic)-encapsulated acitretin nanoparticles for topical and extended treatment

Acitretin is a primary treatment for moderate-to-severe psoriasis, however, the substantial side effects associated with its daily oral administration and relapse after withdrawal significantly restrict its clinical utility. To address this challenge, we designed a transdermal delivery system using hyaluronic acid-based dissolving microneedle patches containing poly (lactic-co-glycolic)-encapsulated acitretin nanoparticles for effective topical drug administration and prolonged therapeutic effects. This microneedle exhibited favorable mechanical properties, which could easily penetrate through the thickened epidermis for intralesional drug delivery. We showed that numbers of acitretin-loaded microspheres were uniformly compacted at the bottom of needle tips, giving the microneedle dense surface morphology required for effective skin penetration, prolonged retention, and sustained release of acitretin both in vitro and in an imiquimod-induced psoriasis in vivo model. A single dose of our transdermal treatment not only alleviated the psoriasis-like skin inflammation in acute phase, but also established a long-term therapeutic effect. Moreover, the transdermal approach proved more effective than daily oral administration of the same dose of free drug, demonstrating less systemic toxicity than oral drug intake or topical cortisol application. This new system offers an innovative way for drug delivery and disease treatment, and also provides an antimicrobial control strategy for a wide range of applications.

Evaluation of Clobetasol and Tacrolimus Treatments in an Imiquimod-Induced Psoriasis Rat Model.

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.

Development and evaluation of methotrexate-loaded nanoemulsion formulation for topical treatment of psoriasis.

Psoriasis is a chronic inflammatory disease that is becoming widespread and is associated with many kinds of additional severe diseases. The present study aimed to develop a methotrexate-loaded almond oil-based nanoemulsion formulation (MTX NE) for topical administration. The drug-loaded nanoemulsion formulation was prepared by high shear homogenization technique. The formulation's stability, as well as other physical and chemical characteristics, including entrapment effectiveness, drug release kinetics, skin permeability, skin irritation, and in vivo evaluation of the optimized formulation, was assessed. Additionally, imiquimod-induced psoriasis in rats was employed to investigate the efficacy of MTX NE against skin disorders. The MTX NE formulation was developed with a particle size of 18.74 ± 9.748nm, a polydispersity index (PDI) of 0.198 ± 0.01, and an average entrapment efficiency of 79.65 ± 3.84%. The release kinetics model estimates 81.08% drug release at pH 5.5 after 24h. The major layers of the skin, the epidermis, and dermis were successfully fluidized by the optimized MTX NE formulation, as shown by FTIR results, most likely enhancing drug retention and permeability. However, since Tween 80 and PEG 400 are well-known penetration enhancers, their application greatly accelerates these effects. Permeation data indicate that after 24h, methotrexate was released from the nano-emulsion at 76.83 ± 4.98g/cm2 with a flux rate of 2.385 ± 0.61µg/cm2/h. The in vivo study conducted on rabbit skin showed that the enhanced skin penetration of the prepared MTX-loaded nanoemulsion formulation does not cause any structural modifications in the inter-cellular lipid layers of the stratum corneum. Rabbits used in the in vivo anti-psoriatic investigation demonstrated that MTX NE produced a 95% reduction in PASI. The pharmacokinetic profile revealed that the Cmax, Tmax, and t1/2 values were 8.63µg/mL, 12.5h, and 17.77 ± 2.21h, respectively. These findings suggest that the formulation MTX NE is effective in treating psoriasis and may reduce psoriasis symptoms.

Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation.

IL-1β is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1β, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1β employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1β and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1β antibody responses that inhibit IL-1β activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1β nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.

Oral Exposure to Low Concentration of Fumonisin B2, but Not Fumonisin B1, Significantly Exacerbates the Pathophysiology of Imiquimod-Induced Psoriasis in Mice.

This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.