Dermal Cell Infiltrate Research Articles

Lichen planus following Covid-19 vaccination: a narrative review.

Lichen planus (LP) is an inflammatory disease that afflicts skin, mucous membranes, cutaneous appendages. Moreover, LP represents a prototype of lichenoid dermatosis, being characterized by the presence of a dense dermal cell infiltrate. Although most cases of LP are idiopathic, infectious and drug-related factors must also be considered in the etiology. In this context, the occurrence of LP and lichenoid drug eruption following different types of vaccination is a possible event. Therefore, the aim of our review is to provide a broad perspective to clinicians by analyzing the current literature cases of LP and lichenoid eruptions following COVID-19 vaccination, also investigating the possible pathogenetic mechanisms underlying this phenomenon. A total of 61 cases of LP and lichenoid eruption following COVID-19 vaccination have been collected. However, the number of cases of LP and lichenoid drug eruption is extremely low if compared to the number of vaccines administered overall, suggesting that the risk of LP and lichenoid eruption following COVID-19 vaccination is extremely low. Certainly, further studies are desirable to identify the population most at risk and the possibility of taking preventive measures.

Role of kinin receptors in skin pigmentation

Previous studies have shown that all kinin system is constitutively expressed in the normal and inflamed skin, with a potential role in both physiological and pathological processes. However, the understanding regarding the involvement of the kinin system in skin pigmentation and pigmentation disorders remains incomplete. In this context, the present study was designed to determine the role of kinins in the Monobenzone (MBZ)-induced vitiligo-like model. Our findings showed that MBZ induces higher local skin depigmentation in kinin receptors knockout mice (KOB1R, KOB2R and KOB1B2R) than in wild type (WT). Remarkably, lower levels of melanin content and reduced ROS generation were detected in KOB1R and KOB2R mice treated with MBZ. In addition, both KOB1R and KOB2R show increased dermal cell infiltrate in vitiligo-like skin, when compared to WT-MBZ. Additionally, lack of B1R was associated with greater skin accumulation of IL-4, IL-6, and IL-17 by MBZ, while KOB1B2R presented lower levels of TNF and IL-1. Of note, the absence of both kinin B1 and B2 receptors demonstrates a protective effect by preventing the increase in polymorphonuclear and mononuclear cell infiltrations, as well as inflammatory cytokine levels induced by MBZ. In addition, in vitro assays confirm that B1R and B2R agonists increase intracellular melanin synthesis, while bradykinin significantly enhanced extracellular melanin levels and proliferation of B16F10 cells. Our findings highlight that the lack of kinin receptors caused more severe depigmentation in the skin, as well as genetic deletion of both B1/B2 receptors seems to be linked with changes in levels of constitutive melanin levels, suggesting the involvement of kinin system in crucial skin pigmentation pathways.

Spontaneous Lesions of Endangered Geriatric Julia Creek Dunnarts (Sminthopsis douglasi, Archer 1979) with Emphasis in Reproductive Pathology.

Julia Creek dunnarts are an endangered species of carnivorous marsupials and the focus of multiple conservation strategies involving significant resources such as captive breeding programs. Despite the relevance for conservation, no study to date has focused on evaluating geriatric diseases in dunnarts. This study describes the pathology findings in a group of one wild and thirty-five captive-born, mostly geriatric Julia Creek dunnarts that failed to produce offspring over multiple breeding periods. A total of 20 females and 16 males were submitted for a postmortem examination, with ages ranging from 9 to 42 and 12 to 42 months for females and males, respectively. Of these, 10 had unremarkable findings. The most common condition in females was cystic glandular hyperplasia (n = 8), typical of hormonal dysregulation profiles in senescence, particularly hyperestrogenism. Rarely, cutaneous disease represented by unidentified dermal round cell infiltrates was observed in females (n = 2). Primary reproductive hormonal dysregulation was also suspected in males diagnosed with testicular degeneration, aspermatogenesis and/or atrophy (n = 3). Cutaneous round cell infiltrates, possibly compatible with epitheliotropic lymphomas, were seen in males (n = 3), and 2/3 affected males also had concurrent testicular degeneration or atrophy, indicating male sex could be a predictor for lymphoid neoplasia in aged dunnarts, especially in individuals with concurrent testosterone-luteinizing hormone dysregulation as it occurs in gonadectomized animals. The role of an underlying viral etiology is also explored. This study is the first to describe major spontaneous diseases in endangered aged Julia Creek dunnarts, providing an important understanding of senescence and geriatric diseases within a conservation context.

Correlations between histopathologic findings, serum biomarker levels, and clinical outcomes in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological emergencies. The role of cytokines and chemokines in the pathogenesis, progression of the disease, and histopathologic features is not fully elucidated. To address this gap, we conducted a retrospective study examining the associations between 42 serum biomarkers, histopathologic findings, and clinical outcomes in SJS/TEN patients. We reviewed the medical records of 23 patients diagnosed with SJS/TEN. Regarding histopathology, our study did not reveal any significant associations between the degree of epidermal necrosis, dermal mononuclear cell infiltration, and clinical outcomes. However, an intriguing observation was made regarding the degree of dermal infiltration of CD8 + cells, which showed a negative correlation with the severity of acute ocular complications. Notably, serum levels of IFN-γ positively correlated with the number of CD8 + cells in dermal infiltration. Additionally, higher serum levels of myeloperoxidase were associated with greater degrees of epidermal necrosis, while serum Fas ligand and stem cell factor levels were elevated in individuals with increased dermal mononuclear cell infiltration. Furthermore, the levels of S100A8/A9 were significantly correlated with the SCORTEN and mortality rate. These findings provide insights into the intricate pathogenesis of the disease.

Lupeol alleviates atopic dermatitis-like skin inflammation in 2,4-dinitrochlorobenzene/Dermatophagoides farinae extract-induced mice

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that affects from children to adults widely, presenting symptoms such as pruritus, erythema, scaling, and dryness. Lupeol, a pentacyclic triterpenoid, has anti-inflammatory and antimicrobial activities. Based on these properties, the therapeutic effects of lupeol on skin disorders have been actively studied. In the present study, we aimed to determine the effectiveness of lupeol on AD.MethodsWe utilized tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated keratinocytes and 2, 4-dinitrochlorobenzene/Dermatophagoides farinae extract (DFE)-induced AD mice to confirm the action.ResultsLupeol inhibited TNF-α/IFN-γ-stimulated keratinocytes activation by reducing the expressions of pro-inflammatory cytokines and chemokines which are mediated by the activation of signaling molecules such as signal transducer and activator of transcription 1, mitogen-activated protein kinases (p38 and ERK), and nuclear factor-κB. Oral administration of lupeol suppressed epidermal and dermal thickening and immune cell infiltration in ear tissue. Immunoglobulin (Ig) E (total and DFE-specific) and IgG2a levels in serum were also reduced by lupeol. The gene expression and protein secretion of T helper (Th) 2 cytokines, Th1 cytokines, and pro-inflammatory cytokine in ear tissue were decreased by lupeol.ConclusionsThese results suggest that lupeol has inhibitory effects on AD-related responses. Therefore, lupeol could be a promising therapeutic agent for AD.

1128 Trametinib treatment causes an increase in disease severity and reduced dermal immune cell infiltration in a mouse model of junctional epidermolysis bullosa

1128 Trametinib treatment causes an increase in disease severity and reduced dermal immune cell infiltration in a mouse model of junctional epidermolysis bullosa

803 Epidermal inflammatory activity is an important driver of hidradenitis suppurativa lesions

Hidradenitis suppurativa (HS) is an inflammatory skin disorder of the pilosebaceous unit defined by painful nodules, tunnels, and scarring. Previous studies documented dermal cell infiltrate and the abundance of inflammatory cytokines in HS lesions, including TNFα, IL-17, and IL-1β. However, not much is currently known about the contribution of keratinocytes and immune cell activity within the epidermis in HS. We found that the degree of epidermal inflammation in HS lesions positively correlated with Hurley stage of disease (r =0.746; p=0), indicating the evolution of epidermal responses with disease severity. Keratinocytes were the primary producers of TNFα (p<0.05) and IL-6 (p<0.05) in HS lesions at all Hurley stages. Increased expression of CXCL3 (5-fold; p<0.01) in keratinocytes of stage III lesions positively correlated with increased recruitment of neutrophils to stage III lesional epidermis. Compared to healthy keratinocytes, enhanced production of chemokines from HS keratinocytes, including CCL22 (stage II 4-fold; p=0.09) and CCL3 (stages II and III p<0.05; 30-fold and 10-fold respectively), was associated with CD8 T cell infiltration and corresponding chemokine receptor expression in the epidermis. These recruited immune cells strongly produce or enable the production of IFNγ (>50 fold), IL-17A (500-fold), and IL-1β (5 to 10-fold), as well as IFNβ1, CXCL10, and STAT1 (HS II/III lesions; p<0.05 for all) by multiple cell types locally in the epidermis, likely generating positive feedback for increased inflammation. As epidermal inflammation evolves during disease progression and contributes to immune cell recruitment, our data suggest that topical therapeutics that block cytokine and chemokine production from the epidermis may be efficacious in HS. In all, our results collectively indicate that keratinocytes are not simply bystanders in HS inflammatory events, but rather actively contribute to HS pathogenesis.

CD8+ mycosis fungoides: A wolf in sheep’s clothing?

Sir, CD8+ mycosis fungoides (MF) is a rare form of MF with an indolent course. Herein, we report a rare case of CD8+ fungoid mycosis preceded by lymphomatoid papulosis type D with an aggressive course. A 36-year-old female presented with several papular lesions on the trunk and extremities with a relapsing–remitting course. Histopathology and an immunohistochemical study confirmed CD8-positive lymphomatoid papulosis type D and methotrexate at 25 mg/week was initiated. After a temporary clinical improvement, the lesions worsened, became infiltrated, and grouped as vaguely annular and angular patches with serpiginous borders (Fig. 1). A second scalp biopsy was performed and a diagnosis of CD8+ MF was established. An extension workup was normal, and MF was classified as stage IB. PUVA therapy was started with acitretin at 25 mg/day. After four weeks from the beginning of treatment, the patches completely disappeared but with the concomitant appearance of four subcutaneous tumors. The evolution was spectacular in fifteen days, with the tumors rapidly increasing in size, becoming ulcerative and necrotic, and one being localized in the left cervical area compressing the upper respiratory tract (Fig. 2). A subsequent biopsy revealed massive epidermal and dermal large cell infiltration (Fig. 3a); the tumor cells were positive for CD3, CD8, and CD7 (Fig. 3b) and negative for CD4, CD5, CD3, CD2, and CD30. Antigen Ki-67 was expressed by more than 80% of T-cells (Fig. 3c). A cerebral and thoraco-abdominal CT scan revealed multiple axillary lymph nodes with hypermetabolism on a PET scan. An osteomedullar biopsy was normal, and lactate dehydrogenase (LDH) was increased to 358 U/L. Chemotherapy was performed, but the patient died after two cycles of CHOEP. In contrast to classical CD4+ mycosis fungoides, CD8+ MF is a rare cytotoxic phenotype constituting about 5% of all cases of MF [1]. It belongs to the first group of primary cytotoxic cutaneous lymphomas (PCCL) with a good prognosis, an indolent course, and a slow progression of the lesions over several years [2]. However, rare cases with a more aggressive course have been reported in the literature [3]. The main differential diagnosis of aggressive CD8+ MF is an aggressive epidermotropic cutaneous CD8+ lymphoma that is a rare cutaneous lymphoma with a poor prognosis due to rapid extracutaneous dissemination [4]. The prognosis of the CD8+ subtype of mycosis fungoides (MF) is controversial. More studies are necessary to clarify this subject.

Mouse models of atopic dermatitis: a critical reappraisal.

Mouse models for atopic dermatitis (AD) are an indispensable preclinical research tool for testing new candidate AD therapeutics and for interrogating AD pathobiology in vivo. In this Viewpoint, we delineate why, unfortunately, none of the currently available so-called "AD" mouse models satisfactorily reflect the clinical complexity of human AD, but imitate more "allergic" or "irriant" contact dermatitis conditions. This limits the predictive value of AD models for clinical outcomes of new tested candidate AD therapeutics and the instructiveness of mouse models for human AD pathophysiology research. Here, we propose to initiate a rational debate on the minimal criteria that a mouse model should meet in order to be considered relevant for human AD. We suggest that valid AD models should at least meet the following criteria: (a) an AD-like epidermal barrier defect with reduced filaggrin expression along with hyperproliferation, hyperplasia; (b) increased epidermal expression of thymic stromal lymphopoietin (TSLP), periostin and/or chemokines such as TARC (CCL17); (c) a characteristic dermal immune cell infiltrate with overexpression of some key cytokines such as IL-4, IL-13, IL-31 and IL-33; (d) distinctive "neurodermatitis" features (sensory skin hyperinnervation, defective beta-adrenergic signalling, neurogenic skin inflammation and triggering or aggravation of AD-like skin lesions by perceived stress); and (e) response of experimentally induced skin lesions to standard AD therapy. Finally, we delineate why humanized AD mouse models (human skin xenotransplants on SCID mice) offer a particularly promising preclinical research alternative to the currently available "AD" mouse models.

313 An oral decaherb formula suppressed Th2 inflammation and improved gut microbiota profile with 16S rRNA sequencing in mice model with atopic dermatitis

Recent studies highlighted the T helper (Th)-2 and systemic nature of atopic dermatitis (AD). In addition, gut microbiota is found to be important in the immune development and regulation in AD. Despite the recent biologics evolution, there are still huge unmet needs in the systemic therapies. Oral herbal medicine has been used in the management of AD for centuries in Asia. An oral decaherb (ten herbs) formula is commonly used as an integrative treatment for AD patients in our center. However, its mechanism of action is unknown. We aimed to investigate its mechanism of action and effect on the gut microbiota in mice model with AD. 2,4-dinitrochlorobenzene (DNCB) was applied over the shaved back of mice to induce atopic dermatitis like skin inflammation. A total of 60 female BALB/c mice were randomly divided into positive/negative control groups and low/mid/high dose decaherb groups. Blood and skin biopsy samples were collected on Day 21. Fecal bacterial DNA were sequenced with V4-V5 region of 16S rRNA gene using MiSeq platform. Raw sequence data were analyzed using QIIME2. Histopathological analysis of the lesional skin revealed a decrease in epidermal thickening, eosinophil and mast cell infiltration in dermis in mid/high dose decaherb groups. Serum IgE and CCL17 were lowered in mid/high dose decaherb groups. Level of mRNA expression of Th2 cytokines including interleukin(IL)-4, IL-13, CCL-17 and IL-31 were reduced in the lesional skin of mid/high decaherb groups. Relative abundance of anti-inflammatory short-chain fatty acids (SCFAs) producing bacteria (Ruminococcaceae, Coprococcus and Bifidobacterium) were increased in mid/high dose decaherb groups. This study suggested that oral decaherb formula suppressed the Th2 inflammation and improved the gut microbiota profile in mice model with AD. Further clinical trial is needed to establish and optimize its therapeutic benefit in our AD patients.

Lues Maligna in an Immune-Reconstituted Patient with Retroviral Infection: A Case Report

Lues Maligna in an Immune-Reconstituted Patient with Retroviral Infection: A Case Report

Ulcerative nodules on the entire body

Ulcerative nodules on the entire body

Chamaejasmine Isolated from Wikstroemia dolichantha Diels Suppresses 2,4-Dinitrofluoro-benzene-Induced Atopic Dermatitis in SKH-1 Hairless Mice.

Plants of the genus Wikstroemia have long been used as traditional medicines to treat diseases like pneumonia, rheumatism, and bronchitis. This study was designed to determine the effect of chamaejasmine, a biflavonoid present in W. dolichantha, on atopic dermatitis (AD)-like skin lesions in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD. Initially, we examined the anti-allergic activities of ten flavonoids from W. dolichantha by measuring β-hexosaminidase release from RBL-2H3 cells. Subsequently, an SKH-1 hairless mouse model of AD was developed based on the topical application of DNCB. Chamaejasmine (0.5%) or pimecrolimus (1%, positive control) were applied to dorsal skins of DNCB-sensitized AD mice for two weeks. Serum IL-4 and IgE levels were determined using enzyme-linked immunosorbent assay kits and transepidermal water loss (TEWL) and skin hydration were measured using a Tewameter TM210 and a SKIN-O-MAT, respectively. Of the ten flavonoids isolated from W. dolichantha, chamaejasmine most potently inhibited DNP-specific IgE-induced degranulation in RBL-2H3 cells. Topical administration of chamaejasmine attenuated the clinical symptoms of DNCB-induced dermatitis (i.e., itching, dryness, erythema, and edema). Histological analyses demonstrated that dermal thickness and mast cell infiltration in dermis were significantly reduced by chamaejasmine. In addition, 0.5% chamaejasmine inhibited DNCB-induced increases in total IL-4 and IgE levels in serum, improved skin barrier function, and increased epidermis moisture. Our findings suggest chamaejasmine might be an effective therapeutic agent for the treatment of atopic diseases.

379 Characterizing the Role of PLCγ2 in Autoantibody-induced Skin Inflammation

Phospholipase Cγ2 (PLCγ2) is an important member of immunoreceptor signaling expressed mostly in haemopoietic cells. Gain-of-function mutations of PLCγ2 have been reported in both mice and human cases causing a complex syndrome involving skin manifestations resembling epidermolysis bullosa. Previously we showed that PLCγ2 deficient mice remained protected in an autoimmune dermatitis model induced by the passive transfer of autoantibodies against collagen type VII (anti-C7), which is a key anchoring fibril in the dermal-epidermal junction. Our aim was to further characterize the mechanisms leading to this phenotype in PLCγ2 deficient mice. Anti-C7 antibody level in blood was tested by ELISA. Histology samples were made followed by H&E and immunostaining. Leukocyte accumulation in ear samples was measured by flow cytometry. Generation of proinflammatory microenvironment in the skin was analysed by ELISA. Anti-C7 IgG was present in the circulation and showed deposition along the dermal-epidermal junction in both genotypes. According to histology and flow cytometry a severe dermal immune cell infiltration, mostly neutrophil accumulation developed in wild type mice with the increase of proinflammatory mediators in the inflamed skin. However, neutrophil infiltration and production of proinflammatory mediators were abrogated in PLCγ2 deficient animals. Taken together, PLCγ2 deficient mice were completely protected from skin inflammation upon anti-C7 treatment. Neutrophil accumulation and the proinflammatory microenvironment failed to develop in the skin in the absence of PLCγ2. These results indicate that PLCγ2 has an essential role creating the proinflammatory milieu after autoantibody deposition in the skin.

Comparison of Clinic - Histopathologic Findings and Morphometric Measurements of Subclinical Laminitic Claws in Dairy Cattle

The aim of this study was to evaluate the clinic-histopathologic characteristics and to compare the morphometric measurements of healthy and subclinical laminitic claws of dairy cattle at different ages and weights. Non-lame 60 Holstein feet randomly collected from the slaughterhouse were evaluated. The effects of age, body-weight, claw location (right front lateal or right front medial etc), and presence of laminitis were investigated. The claws‘ conformation were evaluated morphometrically with ten measurements (toe length, toe height, outer and inner edges of the claw, heel height, the length of heel, the length of diagonal front wall, dorsal hoof angle, the width and the length of the sole). The claws were classified as normal or laminitic according to the histopathologic findings. The clinical findings of laminitis was confirmed on 71.2% of the claws (n=66). The toe length, toe height, the height of outer and inner edges of the claw, heel height, the length of heel, the length of diagonal front wall were smaller in laminitic claws. The dorsal hoof angle of healthy claws were bigger and statistically significant than the laminitic claws. Small haemorrhagic areas were determined in the parietal corium in the laminitic claws comparing to macroscopically healthy claws. The histopathologic characteristics of the corium of laminitic claws involve the hyperaemia, haemorrhages, oedema, thrombosis of capillaries and presence of mononuclear cell infiltration in dermis, stretching epidermal lamella, necrosis of epithelial cells and detachment of the lamellar basement membrane. According to this study results, contrary to literature, there was not a reliable relation between some changes in morphological structure of the claws and the presence of the laminitis were observed.

Role of Histopathology in the Diagnosis of Cutaneous Leishmaniasis: A Case-Control Study in Sri Lanka.

Cutaneous leishmaniasis (CL) displays a spectrum of manifestations clinically and histologically. Then, it becomes a diagnostic challenge and must discern from the other clinical and histological mimics, especially when the Leishman-Donovan bodies are inattentive. In this study, we compared the distinguishing histomorphological characteristics of CL against the other skin diseases with similar clinical and histological features. Skin biopsies of 181 patients, which suspect CL clinically, are evaluated histologically. Pertaining to the first case-control comparison, which performed between skin lesions of CL with or without discernible organisms and the other granulomatous dermatitis, highlighted that the ill-formed coalescent granulomata (OR = 14.83) and diffuse dense dermal plasma cell infiltrate (OR = 74.25) are significantly associated with the skin lesions of CL. The second case-control analysis was between CL without discernible organisms and the other granulomatous dermatitis, and identified a significant association in the presence of ill-formed coalescent granulomata (OR = 16.94) and diffuse dense (>50/HPF) dermal plasma cell infiltrate (OR = 74.5) in the skin lesions of CL. Pertaining to epidermal changes, acanthosis (OR = 2.38), spongiosis (OR = 9.13), and the presence of ulceration (OR = 20.26) are among the major concerns in CL. In conclusion, in the presence of clinical suspicion, dermal granulomata in ill-formed coalescent morphology with high plasma cell density in a diffuse arrangement are positive factors for the diagnosis of CL, especially when the discernible Leishmania amastigotes are absent. Resource utilization such as polymerase chain reaction and other ancillary techniques during the diagnosis of CL can be minimized by using a range of histopathological features and special attention should be focused on this in the future.

Finger necrosis with eosinophilia and symmetrical occlusion of the peripheral artery

Case presentationA 59-year-old man with hypertension, dyslipidemia and a current smoking history had presented with bilateral painful finger ulcers (figure 1A). The patient was referred to our hospital for the...

Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes

BackgroundRosacea is a chronic inflammatory skin disorder of uncertain etiology. Evidence suggests the underlying pathogenesis is modulated by abnormal inflammatory and vascular responses. Thalidomide is a synthetic derivative acid with anti-inflammatory and anti-angiogenic properties. However, its effects on rosacea remain unknown. ObjectivesTo investigate the effects of thalidomide on the lesional alterations and molecular mechanisms in rosacea. MethodsMice were intradermally injected with LL37 to induce rosacea-like features and intraperitoneally administered with thalidomide. The severity of skin inflammation was evaluated. The mRNA levels of cytokines and chemokines associated with rosacea were assessed by qPCR. The number of CD4 positive infiltrated T helper cells and CD31 positive microvessels, and related-genes were measured by immunofluorescence, qPCR and ELISA. Moreover, the effect of thalidomide on inhibiting NF-κB activation was determined by immunofluorescence and western blot. ResultsOur results showed that thalidomide significantly alleviated erythema and reduced inflammatory cell infiltration in dermis of LL37-induced rosacea-like mice. The production of cytokines and chemokines induced by LL37 was decreased by thalidomide in mice skin and HaCaT keratinocytes. Particularly, we showed thalidomide reduced CD4+ T helper cell infiltration and downregulated Th1- and Th17-polarizing genes. In addition, thalidomide treatment lowered the microvessel density and vascular endothelial growth factor (VEGF) expression. We further demonstrated that thalidomide suppressed NF-κB activation in LL37-treated skin and in TNF-α-stimulated HaCaT keratinocytes in vitro. ConclusionsOur findings suggest thalidomide attenuates the inflammation and represses NF-κB activation in skin, which leads to assumptions that thalidomide may be a new therapeutic agent for rosacea.

Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis.

Background:As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.Methods:WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC).Results:Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm2, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm2, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.Conclusions:IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.

Histopathologic Features in Animal Model of Atopic Dermatitis Induced by Topical Application of Oxazolone

Animal models of atopic dermatitis (AD) are widely used to investigate therapeutic effects of candidates for AD. However, the characteristics of each model are not fully understood. This study was designed to compare the animal models of dermatitis induced by dinitrofluorobenzene (DNFB) and oxazolone (Ox). We investigated the effects of DNFB and Ox on skin thicknesses and weights as well as skin lesions associated with AD such as scale, crust and erythematous eruption, and histopathological changes such as hyperkeratosis, dermal and epidermal hyperplasia and immune cell infiltration in inflamed tissues. Multiple application of 0.5% Ox onto the skin increased skin thickness and weight compared to those of DNFB treated mice, as well as those of normal mice. In addition, topical application of DNFB induced marked scale, crust and erythematous eruption, while Ox induced erythematous eruption and mild scale and crust. Histopathological examination revealed that 0.5% Ox induced marked hyperplasia in the dermis and epidermis, large vesicles, spongiotic changes, mild hyperkeratosis and immune cell infiltration in balb/c mice. These data suggest that multiple applications of Ox can induce chronic AD like dermatitis in balb/c mice.