Decreased interleukin‐21 expression in skin and blood in advanced mycosis fungoides

Interleukin (IL)‐21 is regarded as a potent antitumor agent, which increases the cytotoxicity of both natural killer (NK) and CD8⁺ T cells. In this study, we investigated the role of IL‐21 in mycosis fungoides (MF). IL‐21 mRNA expression levels in patch and plaque MF were significantly higher than those in normal skin. IL‐21 mRNA expression levels in tumor MF were significantly decreased compared with those in patch and plaque MF. Interestingly, mRNA expression levels of IL‐21 in MF lesional skin significantly correlated with those of T‐helper type‐1 cytokines/chemokines such as CXCL10, CXCL11 and γ‐interferon. Immunohistochemistry showed that IL‐21 was expressed by keratinocytes in patch and plaque MF. Furthermore, serum IL‐21 levels in patients with tumor MF were significantly lower than those of healthy controls and plaque MF. Thus, IL‐21 expression was significantly downregulated in skin and blood of patients with tumor MF, which may contribute to progression of MF. Our study suggests that recombinant IL‐21 would be a promising therapy for MF.     

Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4+ CD25highFoxP3+ T‐regs cells

Not only macrophages, T‐helper (Th)1 and Th2, but also CD4⁺ CD25^highFoxP3⁺ regulatory T cells (T‐regs) are involved in immune response to Mycobacterium leprae. We aimed to evaluate serum interleukin (IL)‐1β and IL‐12p70 (macrophage cytokines), interferon‐γ (IFN‐γ) (Th1 cytokine), IL‐4 (Th2 cytokine) and circulating CD4⁺ CD25^highFoxP3⁺ T‐regs, in untreated leprosy patients. Forty three patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T‐regs using flow cytometry. Patients were subgrouped into tuberculoid (TT), pure neural leprosy (PNL), borderline cases, lepromatous (LL), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). Serum IL‐12p70, IFN‐γ and IL‐4 were significantly higher in patients versus controls (P < 0.05). Serum IL‐4 was highest in LL and lowest in RL1 (P = 0.003). Serum IL‐1β levels was significantly higher in multibacillary versus paucibacillary patients (P = 0.006). Significantly higher T‐regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(P < 0.001), with significant differences versus controls (P < 0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls (P < 0.05). T‐regs/T‐effs was lowest in ENL(P < 0.05). IFN‐γ correlated positively with T‐regs but negatively with IL‐1β (P = 0.041&0.046 respectively), which correlated positively with T‐effs%( P = 0.05). IL‐4 correlated positively with T‐regs FoxP3 expression% (P = 0.009). We concluded that: Circulating T‐regs were increased in TT, RL1 and PNL patients, known of relatively high cell‐mediated immunity. This finding was supported by low FoxP3 expression (in PNL) and correlation between T‐regs count and IFN‐γ level. Overproduction of IL‐4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T‐regs and increased T‐regs FoxP3 expression%. IL‐1β probably has a pro‐inflammatory role in multibacillary patients as correlated with T‐effs%.     

Impaired T‐cell‐dependent protection against Leishmania major infection in HIV‐positive patients is associated with worsened disease outcome

Cutaneous leishmaniasis (CL) patients coinfected with HIV are known to show a more severe, prolonged course of disease; the immunological basis is not known. We now assessed clinical features, sera and skin biopsies of HIV⁺ and HIV^? patients with CL to identify drivers of increased susceptibility to Leishmania. CL lesion numbers, surface, and healing duration were significantly increased in HIV⁺ as compared to HIV^? patients (2.5, 14 and >4‐fold, respectively). Patients with HIV infection exhibited lower serum Leishmania‐specific IgG levels and decreased IL‐6 and IL‐8. Most importantly, dramatically decreased numbers of CD4⁺ T cells (approximately eightfold), but not CD8⁺ cells, together with fewer CXCR3⁺ Th1 cells, fewer Foxp3⁺ effector/regulatory T cells, and reduced levels of IFN‐γ expression were found in lesional skin. Our findings suggest that compromised CD4⁺ T‐cell responses may be responsible for worsened disease outcome leading to defects in parasite elimination in the absence of sufficient numbers of IFN‐γ‐producing Th1 cells.     

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

The contribution of immune checkpoint receptors in the immunopathogenesis of various autoimmune diseases has been addressed in previous reports. In this study,  the expression profile of T‐cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3) and programmed cell death‐1 (PD‐1) checkpoint molecules was investigated in CD8⁺ T cells of Vitiligo patients. The association of Tim‐3 and PD‐1 expression with disease activity was also explored. The frequency of Tim‐3⁺/PD‐1⁺/CD8⁺ T cells in 30 patients with vitiligo and 30 sex‐ and age‐matched controls was determined by flow cytometry. CD8⁺ T cells were then positively isolated by magnetic beads, and the mRNA expression of PD‐1 and Tim‐3 was determined by TaqMan‐based real‐time PCR. To measure the cytokines production, PBMCs were stimulated with PMA/ionomycin and concentrations of IL‐4, IFN‐γ and TNF‐α were measured in culture supernatants by ELISA. Disease activity of patients with vitiligo was determined using the Vitiligo Area Severity Index. Patients with vitiligo have significantly shown more expression of Tim‐3 and PD‐1 on their CD8⁺ T cells compared with controls. Expression analysis of Tim‐3 mRNA, but not PD‐1, confirmed the results obtained from flow cytometry. While the production levels of TNF‐α and IFN‐γ were found higher by patients with vitiligo, IL‐4 production was lower in patients compared with controls. A direct association was observed between the Tim‐3 and PD‐1 expression and also the production of pro‐inflammatory cytokines with disease activity of patients with vitiligo. Our results indicate that Tim‐3 and PD‐1 are involved in immune dysregulation mechanisms of CD8⁺ T cells in vitiligo and may introduce as potential biomarkers for disease progression and targeted immunotherapy.     

TNF‐α and IL‐10 gene polymorphisms show a weak association with pemphigus vulgaris in the Slovak population

Backround Pemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood. Objective The aim of our case‐control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL‐1α, IL‐1β, IL‐1RI, IL‐1Ra, IL‐4Rα, IL‐12, IFN‐γ, TGF‐β1, TNF‐α, IL‐2, IL‐4, IL‐6 and IL‐10) are associated with pemphigus vulgaris in the Slovak population. Methods DNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) method. Results We found a weak association between pemphigus vulgaris and polymorphic variants in TNF‐α and IL‐10 genes only, with haplotypes TNF‐α–308G/–238G and IL‐10 –1082A/–819C/–592C being significantly overrepresented in pemphigus vulgaris patients (TNF‐α GG: 94.12% vs. 82.86%, P = 0.0216; IL‐10 ACC: 44.12% vs. 30.00%, P = 0.0309). Conclusions Our preliminary results suggest that certain TNF‐α and IL‐10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.     

CD4+ T cells producing interleukin (IL)‐17, IL‐22 and interferon‐γ are major effector T cells in nickel allergy

Background It has been suggested that interleukin (IL)‐17 and IL‐22 play important roles in the elicitation of human allergic contact dermatitis; however, the frequencies of T cell subtypes producing IL‐17 and IL‐22 in human allergic contact dermatitis are unknown. Objectives To determine the frequencies of CD4⁺, CD8⁺ and γδ T cells producing IL‐17, IL‐22 and interferon (IFN)‐γ in the blood and skin from nickel‐allergic patients. Patients/materials/methods Blood samples were collected from 14 patients and 17 controls, and analysed by flow cytometry. Biopsies were taken from 5 patients and 6 controls, and analysed by immunohistochemistry and flow cytometry of skin lymphocytes. Results We found an increased frequency of γδ T cells in the blood, but no differences in the distribution of cytokine‐producing CLA⁺ T cell subtypes in nickel‐allergic patients as compared with controls. In nickel‐allergic patients, there was massive cellular infiltration dominated by CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ in nickel‐challenged skin but not in vehicle‐challenged skin. Conclusion CD4⁺ T cells producing IL‐17, IL‐22 and IFN‐γ are important effector cells in the eczematous reactions of nickel‐induced allergic contact dermatitis in humans.     

Markers of systemic inflammation in psoriasis: a systematic review and meta‐analysis

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)‐1β, IL‐6, IL‐10, C‐reactive protein (CRP), intracellular adhesion molecule (ICAM)‐1, E‐selectin and tumour necrosis factor (TNF)‐α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random‐effects model. Seventy‐eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL‐6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF‐α (d = 1·32, 95% CI 0·86–1·79), E‐selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM‐1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL‐1β and IL‐10 was not significant. Age had a significant effect on the SMD for IL‐6 and TNF‐α. For IL‐6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.     

Interleukin‐10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris

Background Acne is a common chronic inflammatory dermatosis of the pilosebaceous unit. It is characterized by seborrhoea, comedone formation and an inflammatory response consistent with defective cellular immunity to Propionibacterium acnes. Objectives The objective of this study was to investigate the immune reactivity of patients with acne compared with healthy controls by examining the response of peripheral blood mononuclear cells (PBMCs) to stimulation with P. acnes. Particular focus was placed upon measuring the production of interleukin (IL)‐10, which has an established immunoregulatory role. Patients and methods Venous blood was collected from 47 patients with acne and 40 age‐ and sex‐matched healthy controls with no prior history of acne. PBMCs were cultured and their cytokine response to P. acnes investigated. Results Proinflammatory IL‐8 and tumour necrosis factor (TNF)‐α secretion from PBMCs was higher in patients with acne when stimulated with P. acnes. In contrast, a statistically significant reduction in PBMC secretion of anti‐inflammatory IL‐10 in patients with acne was identified. The impaired production of IL‐10 by PBMCs from patients with acne was confined to CD14+ cells presumed to be monocytes. The ability of CD14 cells from patients with acne to phagocytose P. acnes bacteria was also observed to be defective but the addition of exogenous IL‐10 to PBMC cultures restored phagocytic activity. Conclusions These data suggest that patients with acne have a proinflammatory cytokine milieu and crucially are unable to contain early inflammatory changes due to a specific defect in immunosurveillance, namely low monocyte IL‐10 production. Our observations raise the possibility that acne therapeutics might profitably target IL‐10 both as a regulator of proinflammatory cytokines and in augmenting the CD14+ cell phagocytic response.     

IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

Proinflammatory IL‐17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL‐17A in Leishmania‐susceptible BALB/c and artificial overexpression of IL‐17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL‐17A exhibited no phenotype, and IL‐17A and IL‐17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL‐17A and IL‐17F (IL‐17A/F^?/?) in infections with Leishmania major. Interestingly, lesion volumes and parasite burdens were comparable to controls, IL‐17A/F^?/? mice developed a Th1/Tc1 phenotype, and exhibited normal lesion resolution. Thus, in C57BL/6 mice, secretion of IL‐17A and IL‐17F does not influence disease progression. It appears that—depending on the genetic background—cytokines of the IL‐17 family might be responsible for disease progression primarily in susceptible mice.     

Levels of Interleukin‐18 and Endothelin‐1 in Children with Henoch‐Schönlein Purpura: A Study from Northern India

Henoch‐Schönlein purpura (HSP) is an acute systemic vasculitis with unknown etiology, although several studies have found HSP to be related to cytokines such as tumor necrosis factor α, interleukin (IL)‐1, and adhesion molecules. In the present study we determined the levels of cytokines such as IL‐18 and endothelin‐1 (ET‐1) in children with HSP. Subjects were divided into three groups (group 1, 20 subjects with HSP; group 2, 10 subjects belonging to group 1 during their follow‐up 4 to 6 months later; and group 3, 16 controls who were healthy siblings of the subjects). IL‐18 and ET‐1 levels were determined using enzyme immunoassay and expressed as mean ± standard deviation. We observed higher IL‐18 levels in children with HSP (767.6 ± 145.1 pg/mL) than in controls (614.6 ± 66.54 pg/mL, p > 0.05), but IL‐18 levels were found to be significantly lower in subjects with HSP in remission (502.7 ± 60.81 pg/mL) than in those who were in an active phase (1,050 ± 244.5 pg/mL, p < 0.05, n = 10). ET‐1 levels were found to be significantly higher in subjects with HSP (1.93 ± 0.19 pg/mL) than in controls (1.10 ± 0.13 pg/mL, p < 0.05), although no significant difference was observed in ET‐1 levels between subjects in group 1 (1.88 ± 0.30 pg/mL) and group 2 (1.91 ± 0.120, p > 0.05, n = 10). A positive correlation was observed between IL‐18 and ET‐1 levels in subjects with HSP (correlation coefficient [r] = 0.5254, p < 0.01). These results suggest that levels of IL‐18 and ET‐1 are worth monitoring during the clinical course of the disease, but caution must be exercised in extrapolating data based on small study samples.     

Study of pro‐ and anti‐inflammatory cytokine profile in the patients with parthenium dermatitis

Background: Parthenium dermatitis is a common airborne allergic contact dermatitis induced by exposures to the weed Parthenium hysterophorus. The disease manifests as itchy erythematous papules, papulovesicular and plaque lesions on exposed areas of the body. Objectives: The aim of this study was to show the alterations in pro/anti‐inflammatory cytokines in parthenium dermatitis. Methods: The study included 50 patients with parthenium dermatitis confirmed by patch testing using aqueous extracts of P. hysterophorus and 50 age‐matched healthy controls. The levels of pro‐inflammatory [tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐17] and anti‐inflammatory (IL‐4 and IL‐10) cytokines were estimated by commercially available high sensitivity enzyme‐linked immunosorbent assay (ELISA) kits. Results: All the dermatitis patients showed significantly (P < 0.001) elevated levels of TNF‐α, IL‐6, IL‐8, and IL‐17 levels as compared to healthy controls. In contrast, the anti‐inflammatory cytokine IL‐4 showed an insignificant decrease (P < 0.217) and a decrease in level of IL‐10 was statistically significant (0.001) compared with controls. Conclusions: The present study suggests the involvement of pro‐inflammatory cytokines in the pathogenesis of parthenium dermatitis. A decrease in levels of anti‐inflammatory cytokines was demonstrated, which could not downregulate pro‐inflammatory cytokines in parthenium dermatitis.     

Stimulated human melanocytes express and release interleukin‐8, which is inhibited by luteolin: relevance to early vitiligo

Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)‐8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL‐8 production in human melanocytes, and the IL‐8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL‐1β 10 ng/mL, with or without pretreatment with luteolin 50 μmol/L for 30 min, and IL‐8 release was measured by ELISA. Serum cytokines were measured by a microbead array. Skin biopsies were taken from healthy subjects (n = 14) as well as from marginal lesional and nonlesional skin from patients with vitiligo (n = 15). IL‐8 gene expression was evaluated by quantitative real time PCR. Both TNF and IL‐1β stimulated significant IL‐8 release (P < 0.01) from melanocytes, whereas pretreatment with luteolin significantly inhibited this effect (P < 0.01). IL‐8 gene expression was significantly increased in vitiligo compared with control skin (P < 0.05). IL‐8 may be involved in vitiligo inflammation. Inhibition by luteolin of IL‐8 release could be useful for vitiligo therapy.     

Increased interleukin‐36γ expression in skin and sera of patients with atopic dermatitis and mycosis fungoides/Sézary syndrome

Interleukin (IL)‐36γ is expressed by keratinocytes and functions as a key initiator of inflammation in the skin. IL‐36γ expression is enhanced by tumor necrosis factor‐α and IL‐17A, having a strong association with psoriasis. In this study, we examined the role of IL‐36γ in atopic dermatitis (AD) and mycosis fungoides (MF)/Sézary syndrome (SS). Serum levels of IL‐36γ in AD patients and MF/SS patients were elevated compared with those of healthy controls. Importantly, serum IL‐36γ levels in AD patients positively correlated with Eczema Area and Severity Index and those of MF/SS patients positively correlated with serum soluble IL‐2 receptor levels. IL‐36γ mRNA levels in AD skin and MF/SS skin were significantly higher than those of normal skin. IL‐36γ mRNA levels in MF/SS skin positively correlated with IL‐17A mRNA levels. Immunohistochemical staining revealed that IL‐36γ was highly expressed in keratinocytes in lesional skin of AD and MF/SS. Taken together, our study demonstrated that IL‐36γ expression was increased in sera and skin of patients with AD and MF/SS as was reported in psoriatic patients.     

Staphylococcal α‐toxin induces a functional upregulation of TLR‐2 on human peripheral blood monocytes

Resistance to bacterial skin infections, for example with Staphylococcus aureus (S. aureus), is based on the function of intact innate immune mechanisms. Toll‐like receptor (TLR)‐2 recognizes components of S. aureus and is known to be expressed on monocytes. Staphylococcal exotoxins such as staphylococcal enterotoxin B (SEB) or α‐toxin are produced by many S. aureus strains. To investigate TLR‐2 regulation and function on human monocytes upon stimulation with staphylococcal exotoxins to elucidate a putative feedback loop between different staphylococcal components. Monocytes were stimulated with α‐toxin or SEB, respectively. TLR‐2 expression and regulation as well as functional effects of TLR‐2 stimulation with Pam3Cys (TLR‐2/TLR‐1), lipoteichoic acid (LTA) (TLR‐2/TLR‐6) and peptidoglycan (PGN) (TLR‐2 and Nod) were then investigated both at the mRNA and protein level and compared to monocytes from patients with psoriasis. α‐toxin significantly upregulated TLR‐2 expression. TLR‐2 mediated IL‐1β, IL‐6 and IL‐8 secretion was significantly augmented after upregulation with staphylococcal exotoxins. CD36 expression was significantly more downregulated after TLR‐2 upregulation with SEB and consecutive LTA stimulation and TLR‐2 upregulation with α‐toxin following LTA and PGN stimulation, respectively. PGN enhanced CD54 expression after upregulation of the receptor with α‐toxin. Expression of HLA‐DR was unaffected. However, no differences were observed in monocytes from psoriasis patients compared to healthy controls. Together, our findings provide a new link between staphylococcal α‐toxin and TLR‐2 signalling in monocytes which may have implications for skin diseases where skin colonization with S. aureus and dysregulation of TLR‐2 have been described.     

The possible interaction between periostin expressed by cancer stroma and tumor‐associated macrophages in developing mycosis fungoides

Mycosis fungoides (MF) starts as an indolent disease, progresses from a patch stage to confluent plaques and ultimately develops skin tumors. Tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF. The purpose of this study was to elucidate the involvement of TAMs in the lesional skin of different stages of MF. First, we immunohistologically examined the percentage of CD163⁺ macrophages and CD206⁺ cells, as well as the levels of periostin and IL‐4 in cancer stroma. The percentage of CD206⁺ cells increased in parallel with tumor progression, while there was no significant difference in the percentage of CD163⁺ cells. Periostin was prominent in the stromal area at the patch and plaque stages but decreased at the tumor stage. In contrast, IL‐4 was prominently stained at both plaque and tumor stages. To further elucidate the molecular mechanisms of the effects of these stromal factors on TAMs, we examined their effects on mRNA expression in monocyte‐derived macrophages in vitro. Based on microarray analysis and gene ontology, we examined a series of chemokines and MMPs whose expression was strongly connected with periostin stimulation. The DNA microarray results were verified in M2 macrophages using real‐time PCR. We further examined the mRNA expression of these chemokines and MMPs in the presence of periostin and IL‐4 to simulate the advanced stages of MF and validated their protein expression by ELISA. Our present report suggests possible roles of periostin on TAMs in establishing the tumor microenvironment in MF.     

IL1A‐889 C/T gene polymorphism in irritant contact dermatitis

Background Upon skin contact to irritants, interleukin‐1 alpha (IL‐1α) is released in the stratum corneum as a primary step of skin inflammation. Variations in the IL‐1A gene have been shown to alter the expression of IL‐1α. This may influence the susceptibility to skin inflammation and the development of irritant contact dermatitis (ICD). Objective To determine effects of an IL1A‐889 C/T polymorphism in view of susceptibility to develop irritant contact dermatitis. Methods In a case–control study, 478 Caucasian patients with occupational ICD of the hands were genotyped for an IL1A‐889 C/T polymorphism. Results were compared to 393 apprentices from the same high risk occupations (controls). Results Trends of a protective effect of the C→T transition at position IL1A‐889 were seen (OR = 0.81; 95% CI: 0.65–1.00). The genotype distribution for IL1A‐889 was 52.2% wild type (C/C), 39.2% heterozygous (C/T) and 8.6% homozygous for variant allele (T/T) in patients and 46.0%, 42.7% and 11.4% in controls. Subgroup analysis, which took into account atopy status and exposure, did not reveal a significant effect of this polymorphism for an aberrant risk to acquire for ICD. Conclusion Our study indicates a possible protective effect of the IL1A‐889 C/T polymorphism regarding the development of ICD.     

Anti‐IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin‐deficient mice

Please cite this paper as: Anti‐IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin‐deficient mice. Experimental Dermatology 2010; 19: 252–258. Abstract: Sharpin‐deficient (Sharpin^cpdm) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil‐depletion in chronic inflammation, Sharpin^cpdm mice were treated with anti‐IL5 antibodies. Mice treated with anti‐IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham‐treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti‐IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride‐binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti‐IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpin^cpdm mice were crossed with IL5 null mice. Il5^?/?, Sharpin^cpdm/Sharpin^cpdm mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5‐sufficient Sharpin^cpdm mice. The severity of the lesions was similar between IL5‐sufficient and IL5‐deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpin^cpdm mice and suggest that eosinophils have both pro‐inflammatory and anti‐inflammatory roles in the skin of these mice.     

Role of the subgroups of T,B, natural killer lymphocyte and serum levels of interleukin‐15, interleukin‐21 and immunoglobulin E in the pathogenesis of urticaria

The immunological characterization in the pathogenesis of urticaria, mainly regarding cytokine profile, needs more investigation. In this study, subgroups of the T, B and natural killer (NK) lymphocyte from peripheral blood and serum levels of interleukin (IL)‐15, IL‐21 and immunoglobulin (Ig)E were examined in patients with acute urticaria (AU) and chronic urticaria (CU). Moreover, symptom scores and course of the patients were assessed. The percentage of NK cells and the ratio of CD4⁺/CD8⁺ increased, however, CD8⁺ decreased in CU compared to controls (P < 0.01). But no significant changes of T, B and NK lymphocyte were found in AU. IL‐15 and IL‐21 significantly decreased in AU and CU, but IgE increased. CU with a positive autologous serum skin test were more likely to be associated with longer course and higher CD3⁺, B cells and IL‐21, and lower IgE (P < 0.01). Weak negative correlations were demonstrated between CD3⁺, CD8⁺ and scores in CU (r = ?0.23, ?0.25, P < 0.05). Significant correlations were found between B cells and scores and course in CU (r = 0.49, 0.65, P < 0.01). Moreover, a significant correlation was found between IL‐21 and IgE (r = 0.42, P < 0.01) in CU. But no significant correlations were found in AU. Our findings supported the concept that both humoral immunity and cellular immunity dysregulation in the pathogenesis of urticaria – mainly related to the decrease of the serum levels of IL‐15 and IL‐21 – may induce the increasing expression of IgE produced by B cells.     

Peroxisome proliferator‐activated receptor gamma,a possible culprit in mycosis fungoides: an immunohistochemical study

Background It still remains debatable whether peroxisome proliferator‐activated receptor gamma (PPARγ) is pro‐ or antineoplastic, and its exact role in mycosis fungoides (MF) remains unclear. Objective This prospective comparative study aimed to investigate the expression of PPARγ in MF and compare it with psoriatics and controls in a trial to deduce its possible role in MF. Also, we tried to clarify the relation between PPARγ and Bcl‐2 in MF. Methods Twenty MF patients, 20 psoriatic patients and 20 controls were included. All participants underwent a skin biopsy, and immunohistochemical staining for both PPARγ and Bcl‐2 were performed. Western blot analysis was performed for detection of both PPARγ and Bcl‐2. Results The mean area per cent of PPARγ measured in the MF patients (57.1217 ± 9.502417) was significantly higher (P < 0.001) when compared with that of both the psoriatics (2.989 ± 1.723) and controls (35.9357 ± 8.1789). The mean area per cent of Bcl‐2 in MF patients (9.3763 ± 6.6328) was significantly higher (P < 0.001) than that of both the psoriatics (2.35 ± 1.35) and the controls (0.73105 ± 0.5302)]. Our results were confirmed using the western blot analysis. We detected a highly significant positive correlation between the PPARγ and Bcl‐2 mean area per cents in all patients. In our MF patients, both parameters were also positively correlated with the age of the patient, duration and stage of MF (P < 0.05). Conclusion Our data suggest a possible role for PPARγ in the pathogenesis of MF possibly through several mechanisms, one of which might be conferring upon the lymphoma cells, a survival advantage at least partially through up regulating Bcl‐2.