Serum 5-S-cysteinyldopa levels in patients with psoriasis undergoing narrowband ultraviolet B phototherapy

Background. Ultraviolet (UV) B radiation from sunlight can result in tanning or burning of the skin. Narrowband UVB (NB‐UVB), a relatively new light source that is not yet widely available, is effective for treating generalized psoriasis without the use of psoralens. Aims. The melanin‐related metabolite 5‐S‐cysteinyldopa (5‐S‐CD), which reflects pheomelanin production, has been used as a biological marker of melanoma progression, but there are no studies available on therapeutic UVB effects on serum 5‐S‐CD of human subjects. In the present study, we measured the time course of changes in serum levels of 5‐S‐CD in patients with psoriasis undergoing NB‐UVB phototherapy. Methods. In total, 11 Japanese patients with generalized psoriasis vulgaris received NB‐UVB treatment five times per week, at an initial dose of 0.1 J/cm². The dose was increased by 10–20% per treatment for > 20 treatments. Serum samples were taken before and 3, 7, 10, 14 and 28 days after phototherapy. Results. After 4 weeks of NB‐UVB treatment, 9 of 11 patients were in remission, confirming the effectiveness of NB‐UVB for treating Japanese patients with psoriasis. Two patients withdrew before day 28 because of other complications. Mean level of 5‐S‐CD in serum was significantly increased on day 7, 10 14 and 28 compared with the level before phototherapy and it peaked on day 10. Conclusions. Serum 5‐S‐CD levels were significantly increased by therapeutic UVB exposure. Sustained levels of 5‐S‐CD in serum appear to reflect the degree of skin injury during NB‐UVB phototherapy.     

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB‐UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB‐UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB‐UVB exposures on the whole body, given three times a week. Serum calcidiol (25‐hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real‐time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L^?1). NB‐UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L^?1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L^?1 (95% CI 55·4–80·1) in AD and 90·7 nmol L^?1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β‐defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB‐UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB‐UVB caused a marked but nonsignificant decrease of interleukin (IL)‐1β and IL‐17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB‐UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.     

Osteopontin deficiency affects imiquimod‐induced psoriasis‐like murine skin inflammation and lymphocyte distribution in skin,draining lymph nodes and spleen

Osteopontin (OPN) that enhances autoimmunity is expressed in psoriasis lesions; however, its functions in psoriatic inflammation are unknown. We investigated the role of OPN in OPN deficient mice (OPN?/?) by inducing psoriasis‐like inflammation through skin application of imiquimod (IMQ). OPN?/? mice treated with IMQ showed delayed onset ear swelling and attracted less inflammatory cells to the skin. IMQ‐induced lymph node swelling was reduced in the absence of OPN, and IMQ‐mediated expansion of B cells was inhibited. Further, reduction of CD4⁺ T‐cell numbers by IMQ in lymph nodes was suppressed in OPN?/? mice, with an increase in the CD4/CD8 ratio. A comparable pattern was found in spleen. Importantly, IMQ‐induced IL‐17 and IL‐4 expression by CD4⁺ lymph node T cells was reduced in OPN?/? mice. In conclusion, OPN may modulate psoriasis‐like inflammation through altering lymphocyte distribution in skin and draining lymph nodes and by inducing IL‐17 expression of inflammatory T cells.     

Effect of narrowband ultraviolet B therapy on inflammatory markers and body fat composition in moderate to severe psoriasis

Background Previous studies have shown increased prevalence of metabolic syndrome in patients with psoriasis. Objectives To characterize the anthropometric and metabolic profile of Spanish patients with moderate to severe psoriasis compared with controls without psoriasis matched for gender, age and body mass index (BMI), and to evaluate the impact of narrowband ultraviolet B (NB‐UVB) therapy on patient profiles. Methods Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine, vitamins D, B₆ and B₁₂ and folic acid of 50 patients with psoriasis and 50 matched controls were recorded then evaluated after NB‐UVB in patients with psoriasis and correlated with clinical outcome. Results Despite very similar BMIs, 54% of patients met International Diabetes Foundation criteria for metabolic syndrome compared with 42% of controls (P = 0·01); body fat was 29·9% in patients and 28·0% in controls (P = 0·037), correlating with waist circumference; while patient atherogenic profiles were less favourable, with higher apolipoprotein B and low density lipoprotein cholesterol than controls, and both patients and controls showed insufficient vitamin D serum levels (< 20 ng mL^?1). Mean improvement of Psoriasis Area and Severity Index (PASI) after NB‐UVB was 78·2%. Ferritin, B₁₂ and C‐reactive protein decreased significantly after NB‐UVB therapy. Vitamin D levels reached adequate levels after phototherapy; however, no relationship with PASI improvement was observed. Conclusions We characterized inflammatory and atherogenic profiles of Spanish patients with psoriasis compared with matched controls. After NB‐UVB therapy we demonstrated improvement in psoriasis and some systemic inflammation markers, which were not mediated by enhancement of vitamin D synthesis.     

Bath psoralen+ultraviolet A photochemotherapy vs. narrow band‐ultraviolet B in psoriasis: a comparison of clinical outcome and effect on circulating T‐helper and T‐suppressor/cytotoxic cells

Background: Comparative success rates of bath psoralen+ultraviolet A (PUVA) and narrow band‐ultraviolet B (NB‐UVB) in psoriasis treatment are variably reported with no previous studies on the possible effect of bath PUVA on circulating CD4+ and CD8+ T cells. Objective: We aimed to compare the effect of bath PUVA and NB‐UVB clinically and on circulating T‐helper and T‐suppressor/cytotoxic cells in psoriasis. Patients and methods: Thirty‐four psoriatic patients divided into a bath PUVA‐treated group (18 patients) and a NB‐UVB‐treated group (16 patients) were compared regarding the disease severity by psoriasis area and severity index (PASI) score and percentage of circulating CD4+ and CD8+ T cells by flowcytometry before and after treatment. Results: After treatment, the bath PUVA group showed a significantly higher reduction of PASI score (85.44%) than the NB‐UVB group (58.72%). Mean peripheral CD4+ T‐cell percentage was significantly lower after [36.8; 95% confidence interval (CI) 33.80, 39.97] compared with before treatment (42.06; 95% CI 38.29, 45.83) (P<0.05) in the bath PUVA group while this difference was insignificant in the NB‐UVB group (P>0.05). Conclusion: Bath PUVA therapy is superior to NB‐UVB in the treatment of moderate and severe psoriasis with mild reversible side effects. Both modalities have a systemic effect decreasing peripheral CD4+ T cells, which is more with bath PUVA.     

Toll‐like receptor 2 mediates a cutaneous reaction induced by repetitive ultraviolet B irradiation in C57/BL6 mice in vivo

Toll‐like receptors (TLRs) mediate not only innate immunity against infection and but also sterile inflammation triggered by endogenous molecules. We conducted a comparative study of the different inflammatory responses induced by repetitive ultraviolet (UV) B irradiation in wild‐type (WT) and TLR2 knockout (KO) mice, to provide in vivo evidence of the role of TLRs in mediating UVB‐induced responses. UVB‐induced inflammatory responses were less severe in TLR2 KO mice than in WT mice after 6 weeks of repeated UVB irradiation. UVB‐treated TLR2 KO mice displayed less prominent erythema and scaling, and histopathology showed significantly thinner skin and less inflammatory cell infiltration than that in WT mice. UVB‐induced expression of heat‐shock protein 70 (an endogenous ligand of TLR2) was lower in TLR2 KO mice. Quantitative RT‐PCR revealed significantly lower gene expression levels of UVB‐induced interleukin (IL)‐1β, IL‐6 and matrix metalloproteinase (MMP)‐13 in TLR2 KO mice. TLR2 KO mice also showed significantly lower protein level expression of UVB‐induced IL‐1β in ELISA and MMP‐13 in Western blots. Our study demonstrated that TLR2 was associated with inflammatory responses to repetitive UVB irradiation in C57/BL6 mice. Moreover, it suggests that the role of TLR2 in the cutaneous response of UV irradiation and in developing new agents for modulating the effects of UV irradiation should be considered.     

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration

Summary Background A short course of narrowband ultraviolet B (NB‐UVB) exposures increases the serum 25‐hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects. Objectives To compare the effects of NB‐UVB and oral vitamin D substitution in healthy subjects in winter. Methods Healthy adult hospital employees and medical students were screened for serum 25(OH)D concentration. Those with 25(OH)D below 75 nmol L^?1 were randomly given either 12 NB‐UVB exposures or 20 μg of oral cholecalciferol daily for 4 weeks. The NB‐UVB exposures were given with a Waldmann UV 7001 cabin and the mean cumulative dose was 48·4 standard erythema doses. Serum 25(OH)D was measured before and after the treatments by radioimmunoassay. Results The baseline serum 25(OH)D concentrations were 52·9 ± 10·4 (mean ± SD) in the 33 NB‐UVB‐treated and 53·5 ± 12·7 nmol L^?1 in the 30 oral cholecalciferol‐treated subjects. The mean increase in serum 25(OH)D was 41·0 nmol L^?1 [95% confidence interval (CI) 34·8–47·2; P < 0·001] in the NB‐UVB group and 20·2 nmol L^?1 (95% CI 14·6–26·0; P < 0·001) in the cholecalciferol group. The difference between the two treatments was significant at 2 weeks (P = 0·033) and at 4 weeks (P < 0·001). One month after the treatments the 25(OH)D concentrations had increased further. Conclusions The present study shows that 12 NB‐UVB exposures given during 4 weeks increase serum 25(OH)D concentration significantly more than 20 μg of oral cholecalciferol daily. A short NB‐UVB course is an effective way to improve vitamin D balance in winter and the response is still evident 2 months after the course.     

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P = 0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.     

Influence of narrowband ultraviolet B phototherapy on serum tumour necrosis factor‐like weak inducer of apoptosis (TWEAK) in patients with psoriasis

Psoriasis is characterized by keratinocyte resistance to apoptosis. We recently demonstrated an increase in serum tumour necrosis factor‐like weak inducer of apoptosis (TWEAK) in patients after topical treatment for psoriasis. We decided to verify whether narrowband ultraviolet B (NB‐UVB) has a similar effect. Serum concentration of TWEAK was estimated in patients with exacerbated plaque psoriasis treated with NB‐UVB. Baseline TWEAK levels were similar in patients with psoriasis and healthy controls, and Psoriasis Area and Severity Index (PASI) correlated inversely with TWEAK levels. Treatment with NB‐UVB caused a significant reduction in PASI and concurrent increase in serum TWEAK. This finding may be due to increased expression of TWEAK receptor in psoriatic skin, which has been reported previously, with consequent binding of excess soluble TWEAK during treatment and subsequent release after treatment. Severity of plaque psoriasis and its improvement after NB‐UVB treatment may be associated with TWEAK concentrations. The importance of our findings remains to be established.     

Intercellular pathway through hyaluronic acid in UVB‐induced inflammation

Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB‐induced inflammation was not induced in gp91phox‐depleted mice. To test whether gp91phox is directly involved in UVB‐induced inflammation, neutrophil‐ and hyaluronic acid–depleted mice were also irradiated and examined for their response. Hyaluronic acid–depleted mice showed strongly inhibited UVB‐induced inflammation, but the neutrophil‐depleted mice did not exhibit any suppressed UVB‐induced inflammation. To elucidate the pathway by which UVB irradiation induced inflammation, we examined the expression of nucleotide‐binding domain, leucine‐rich‐containing family, pyrin domain‐containing‐3 (NLRP3) and caspase‐1 in the mouse skin. An increase in the expression of NLRP3 and caspase‐1 was seen following the UVB irradiation of C57BL mice; however, the UVB‐irradiated gp91phox‐knockout (gp91phox^?/?) mice did not have this increase in expression. Furthermore, the plasma IL‐1β level increased after the UVB irradiation in C57BL mice, but there was no change in the gp91phox^?/? mice. These results clearly indicate that nicotinamide adenine dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of hyaluronic acid induced by UVB irradiation, and as result, the generation of reactive oxygen species (ROS) increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase‐1, which subsequently increases IL‐1β, thereby finally inducing inflammation. It is thought that this system may play an important role in the damage and ageing of skin, and further studies are necessary to confirm these finding.     

Topical 8-methoxypsoralen enhances the therapeutic results of targeted narrowband ultraviolet B phototherapy for plaque-type psoriasis

Targeted broadband ultraviolet B (UVB) phototherapy as well as 308‐nm excimer laser have been reported to significantly improve or clear localized psoriatic plaques within 5 to 10 treatments when medium fluences [i.e. 4–6 multiples of minimal erythema doses (MED)] were used. Our study was conducted to determine the effects of different concentrations of topical 8‐methoxypsoralen (8‐MOP) cream when used in combination with targeted UV phototherapy with regard to number of treatments and cumulative UV doses to clear localized psoriasis. Ten evaluable patients with stable plaque‐type psoriasis completed the study. Three different concentrations of 8‐MOP creams (0.001%, 0.01% and 0.1%) were applied prior to irradiation with 4 MEDs of targeted narrowband UVB (NB‐UVB), whereas 0.001% 8‐MOP cream was used in conjunction with 5 J/cm² UVA. All irradiations took place once weekly for 12 weeks. Psoriasis severity index (PSI) score was used to evaluate the efficacy of the treatment. With area‐under‐the‐curve analysis, 0.1% 8‐MOP/NB‐UVB was superior to other modalities in reducing the PSI scores. The number of treatments and cumulative NB‐UVB doses necessary to achieve PSI‐95, a 95% reduction in the scores, was also lower in the 0.1% 8‐MOP/NB‐UVB group, although the differences were not statistically significant. We conclude that topical 8‐MOP cream enhances the therapeutic effects of targeted NB‐UVB phototherapy without significantly increasing the short‐term adverse effects.     

Loss of INK4a/Arf gene enhances ultraviolet radiation‐induced cutaneous tumor development

The CDKN2A locus encodes for tumor suppressor genes p16^INK4a and p14^Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation‐induced skin tumors. Panels of INK4a/Arf^‐/? mice and wild‐type (WT) mice were treated with a single dose of UVB (200 mJ/cm²). For long‐term studies, these mice were irradiated with UVB (200 mJ/cm²) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8‐dihydroxyguanosine (8‐oxo‐dG) lesions in INK4a/Arf^?/? mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf^?/‐ mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)‐κB, cyclooxygenase‐2 (COX‐2), prostaglandin E₂ (PGE₂) and its receptors both in UVB‐exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf^‐/‐ mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b⁺Gr1⁺ myeloid cells were present in UVB‐exposed INK4a/Arf^‐/‐ mice compared to WT mice. Our data indicate that by targeting UVB‐induced inflammation, it may be possible to prevent UVB‐induced skin tumors in individuals that carry CDKN2A mutation.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.     

Narrowband ultraviolet B course improves vitamin D balance in women in winter

Background Vitamin D insufficiency is common in winter in the Nordic countries. Objectives  To examine whether a short course of narrowband ultraviolet B (NB‐UVB) improves vitamin D balance. Methods Fifty‐six healthy, white women (mean age 41 years) volunteered and 53 completed the study. NB‐UVB exposures were given on seven consecutive days either on the whole body (n = 19), on the head and arms (n = 9) or on the abdomen (n = 14). Similarly, seven solar simulator exposures were given on the face and arms (n = 11). The cumulative UVB dose was 13 standard erythema doses in all regimens. Serum calcidiol (25‐hydroxyvitamin D) concentration was measured by radioimmunoassay before and after the NB‐UVB exposures. Follow‐up samples were taken from the whole‐body NB‐UVB group at 2 months. Results At onset 41 women (77%) had vitamin D insufficiency (calcidiol < 50 nmol L^?1) and six (11%) had vitamin D deficiency (calcidiol < 25 nmol L^?1). Calcidiol concentration increased significantly, by a mean of 11·4 nmol L^?1 when NB‐UVB was given on the whole body, by 11·0 nmol L^?1 when given on the head and arms and by 4·0 nmol L^?1 when given on the abdomen. Solar simulator exposures given on the face and arms increased calcidiol by 3·8 nmol L^?1. After 2 months serum calcidiol was still higher than initially in the group who received NB‐UVB exposures on the whole body. Conclusions NB‐UVB exposures given on seven consecutive days on different skin areas of healthy women significantly improved serum calcidiol concentration. A short low‐dose NB‐UVB course can improve vitamin D balance in winter.     

Serum miRNA expression profiles change in autoimmune vitiligo in mice

It is widely believed that non‐segmental vitiligo results from the autoimmune destruction of melanocytes. MicroRNAs (miRNAs), a class of small non‐coding RNAs that negatively regulate gene expression, are involved in the immune cell development and function and regulate the development of autoimmune diseases. Recent studies demonstrate that functional miRNAs can be detected in the serum and serve as biomarkers of various diseases. In the present study, we used a mouse autoimmune vitiligo model, in which melanocyte autoreactive CD4⁺ T cells were adoptively transferred into Rag1^?/? host mice. Serum miRNA expression was profiled in vitiligo developed mice and control mice using TaqMan RT‐PCR arrays. We have found that the expressions of 20 serum miRNAs were changed in vitiligo mice compared to control mice. Three increased miRNAs, miR‐146a, miR‐191, and miR‐342‐3p, were further confirmed by a single TaqMan RT‐PCR. Our findings suggest that miRNAs may be involved in vitiligo development and serum miRNAs could serve as serum biomarkers for vitiligo in mice.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

Interleukin‐21 receptor signalling is not critically required for imiquimod‐induced psoriasiform dermatitis in mice

Psoriasis is largely mediated by interleukin (IL)‐23/T helper (Th) 17 axis, and IL‐21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL‐21 in human psoriasis, we found that IL‐21 receptor (IL‐21R) signalling was not crucial for imiquimod‐induced psoriatic inflammation, using IL‐21R^?/? mice. The severity of imiquimod‐induced psoriatic manifestation and pro‐inflammatory Th17 cytokine levels, IL‐17A‐producing γδ T cells and CD4+ T cells, and in vitro IL‐17A production by γδ T cells after IL‐23 stimulation was comparable between wild‐type and IL‐21R^?/? mice. Collectively, IL‐21R signalling was not critically involved in IMQ‐induced psoriatic inflammation despite an increased IL‐21 expression in the IMQ‐treated mouse skin. Our data may represent the significant differences between human psoriasis and murine psoriasis model, and further studies using other models will be required to elucidate the role of IL‐21 in psoriasis pathogenesis.