For generation of memory T cells, mice were first immunized i.p. with 100 μL of emulsion consisting of CFA and 10 nmoles OVA protein, followed by two boosts with the same dose of Ag and Incomplete Freund Adjuvant keeping 10 day intervals. Ten days after the last injection, endogenous IL-2 responses of harvested splenocytes were analyzed by ELISPOT. An ELISPOT assay was carried out as described [45]. Cells isolated from spleens of immunized mice were suspended in

DMEM-10 culture media and restimulated with ovalbumin protein (10 μM). The cells were then cultured for 24 h Compound Library solubility dmso (37°C and 5% CO2 concentration). After incubation, a plate was extensively washed and incubated with the secondary biotinylated antimouse IL-2 Ab (2 μg/mL in 1% BSA in PBS) and streptavidin-alkaline phosphatase (1:1000 in 1% BSA in PBS) followed by detection with alkaline-phosphate substrate (BCIP/NBT). Plates were precisely enumerated using an ELISPOT reader from Cellular Technology Ltd. with dedicated software. All single experiments involved 3–5 mice per group and were repeated at least three times. The data were expressed as means ± SD. Statistical analysis was performed with Student t-test using GraphPad Prism statistical software. p Values < 0.05 were considered as a significant. This work was supported

by National Institutes of Health grant nos. R01AI061077 (to W.S.), R01AI073718 Roxadustat order (to W.S.), and Leukemia & Lymphoma Society Scholar (W.S.) and Special Methisazone Fellow (D.B.G.) awards. R.J.X was supported by NIH grants DK043351 and HL088297. The authors declare no financial or commercial conflicts of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should

be addressed to the authors. Figure S1. Dlg1 is completely deleted in T-cell lineage of KO mice. Splenocytes from KO and WT mice (Vav1-Cre Dlg1flox/flox and Vav1-Cre Dlg1flox/+ respectively) were stimulated with polyclonal mitogen (ConA) overnight, subsequently harvested and lysed. Lysates were separated on 8% SDS-PAGE following by incubation with Dlg1 antibody to evaluate the expression of Dlg1 protein. Brain lysate was used as positive control whereas ERK expression was used as a loading control. Results are representative of three independent experiments. Figure S2. Dlg1 is dispensable for T-cell development in Lck-Cre and Vav1-Cre KO and WT mice. Lck-Cre and Vav1-Cre thymocytes from WT and KO were stained with indicated markers to analyze all thymocyte subsets. No differences in thymocyte subsets were found between WT and KO mice. Results are representative of n>20 mice. Figure S3. Dlg1 is dispensable for thymocyte selection in HY mice.

The A7 DbNPCD8+ and DbPACD8+ sets were of similar magnitude following both primary and secondary infection. This might reflect an inefficient recruitment of suboptimal DbNP366-specific TCRβ after

challenge in A7 transgenics. The extent of TCRβ diversity for DbNP366 was very low and consisted of approximately two clonotypes per A7 mouse PS-341 for the now dominant Vβ4+ (∼50% of DbNPCD8+ TCR). Recruitment of such reduced clontotypic diversity in A7 transgenics was clearly insufficient to drive the full potential of the secondary DbNPCD8+ response and maintain the characteristic DbNPCD8+>>DbPACD8+ hierarchy. The fact that TCRβ clonotype selection changed dramatically for DbNP366 (but Selleckchem SCH772984 not DbPA224) in the A7 mice, no doubt reflects preferential pairing with specific Vα chains, particularly a public Vα17 16. It appears that the public DbNPVβ8.3+CD8+ T cells might be missing in A7 animals because the preferred α-chain partner is missing. Although the α-chain repertoire is diverse in the DbNPCD8+ T cells in terms of CDR3α composition and Jα usage, the response is restricted in variable gene of choice. In B6 mice, the public Vβ8.3 often pairs with Vα17 16. This pairing would be lost in the A7 (Vα2) transgenic mouse. Although the pairing of public DbNP TCRβs with different private Vα chains can be achieved

in vitro, this results in markedly reduced “suboptimal” TCR avidity and IL-2 production 16. Defining what “optimal” means in this context may best be achieved by structural analysis of a variety of more or less “effective” pMHC-I complexes. The present analysis may thus be useful for the later comparison of “best binding” versus “just adequate” interactions at the stochiometric 3-oxoacyl-(acyl-carrier-protein) reductase level. Future studies are needed to determine physiological and pathological consequences of such “just adequate” CD8+ T-cell responses. Even if the normally public Vβ8.3 DbNP366-specific TCR could pair with a KbOVA257-specific

Vα2, many of the resultant TCR heterodimers may not be selected into the immune response due to their low pMHCI affinity threshold 35. A significant proportion of the DbNP (within Vβ4) and DbPA (within Vβ7) TCRβ clonotypes that are prominent in A7 transgenics were, however, detected previously in the wt B6 response. These may represent specific TCRβ that can pair with an irrelevant KbOVA257 Vα2 TCR chain and still display functional TCRαβ heterodimers with sufficient pMHC-I affinity to recruit naïve T cells into the influenza-specific immune response. Given, though, the other, early evidence presented here that alternative TCR Vα chains are sometimes used in the DbNP366 response by tetramer+ CTL that express cell-surface Vα2, we must be cautious not to over-interpret, beyond the finding that the DbNP366-specific T cells respond sub-optimally.

[96] In the case of immunoglobulin light chain and TCRA that lacks the D gene segments, the secondary rearrangement occurs between unrearranged V gene segments upstream and J segments downstream with deletion of the original rearranged VJ segment. These rearrangements do not violate the 12/23 rule. However, buy Talazoparib in the case of IgH and TCRB, rearranged gene contains

a D segment and all other unused D segments are lost during DJ and VDJ rearrangements leaving behind only non-compatible RSSs. This obstacle is overcome by the presence of a 3′ sequence of the V segment, which plays the role of a surrogate RSS, thereby replacing the previously rearranged V, while retaining the already rearranged DJ.[96, 97] RAGs have been shown to exhibit

learn more transposition activity by integrating excised RSS-flanked signal ends into a target DNA molecule, in vitro. Integration can be intermolecular wherein the target DNA is a plasmid or intramolecular in which the target can be the intervening sequence stretching between RSSs.[98-100] Integration was not sequence-specific but was targeted to altered DNA structures like hairpins.[101] Several lines of studies compared RAGs with bacterial transposons and revealed striking similarities.[102] Isolated studies have shown that RAG transposition can occur in vivo.[103, 104] The first among these demonstrated interchromosomal transpositions, wherein TCR-α signal ends from chromosome 14 inserted into the X-linked hypoxanthine-guanine phosphoribosyl transferase locus, resulted in gene inactivation.[103] It was also shown that RAG expression in yeast could lead to transposition.[104] The transib transposase from the insect Helicoverpa zea was shown to be active in vitro and its breakage and joining activities mimicked that of RAG, providing strong evidence that RAGs and transib Thymidylate synthase transposases were derived from a common progenitor.[105] However, there is no evidence that RAG-mediated transposition can occur in the mammalian genome. This can be the result of the stringent regulation of the process in the mammalian system.[106] In contrast

to the standard function of being a recombinase, later studies pointed out that the RAG complex can also act as a structure-specific nuclease and this property has several implications in the pathological roles of the RAG complex (Fig. 4). Studies suggested that RAGs possess a structure-specific 3′ flap endonuclease activity that can remove single-strand (ss) extensions from branched DNA structures.[107] RAGs also showed hairpin opening activity in the presence of MnCl2.[108, 109] The fragility of the BCL2 major breakpoint region was attributed to its acquiring a stable non-B DNA structure in the genome, which was prone to RAG cleavage.[110] Further, it was shown that RAGs could cleave symmetric bubbles, heterologous loops and potential G-quadruplex structures at the physiological concentrations of MgCl2[111, 112] (Fig. 4).

Other studies have demonstrated that helminth infections or antigens down-regulate the allergic response through the action of regulatory T cells, rather than by altering the Th1/Th2 balance [23,38]. In conclusion, we showed that S. mansoni antigens Sm22·6, PIII and Sm29 are

able to down-modulate the inflammatory response in a model of allergic airway inflammation and we suggest that the CD4+FoxP3+ T cells might be involved in this modulation. Studies evaluating other mechanisms underlying the modulatory effect of S. mansoni antigens on the allergic inflammation are in progress; they may X-396 clinical trial contribute to the development of new strategies to prevent allergic diseases. We thank Dr Mauro Teixeira and Dr Geovanni Cassali for their support in the development of this work. We also thank Dr Michele M. Barsante (in memoriam) for her participation in this study and Charles Daniel Schnorr for the review of the text. This work was supported by the Brazilian National Research Council (CNPq). M. I. A., S. C. O. and E. M. C. are investigators supported by CNPq. The authors have no financial conflict of interest.

“
“Through pattern recognition receptors the innate immune system detects disruption of the normal function of the organism and initiates responses directed selleck products at correcting these derangements. Cellular damage from microbial or non-microbial insults causes the activation of nucleotide-binding domain leucine-rich repeat containing receptors in multiprotein complexes called inflammasomes. Here we discuss the role of the NLRP3 inflammasome in the recognition of cellular damage and the initiation of sterile inflammatory responses. The innate immune system possesses multiple families of germline Cediranib (AZD2171) encoded PRR 1. These include TLR, nucleotide-binding domain leucine-rich repeat containing receptors (NLR), RIG-I-like RNA helicases and C-type lectin receptors. These receptors recognize conserved moieties associated with either

cellular damage (DAMP; danger-associated molecular patterns) or invading organisms (PAMP). Activation of these receptors ultimately leads to the production of cytokines that drive the inflammatory response. The NLR family of molecules is a recently described group of intracellular receptors with a unique domain architecture consisting of a central nucleotide-binding domain called the NACHT domain that is located between an N-terminal effector domain and a C-terminal leucine-rich repeat domain 2, 3. The leucine-rich repeat domain serves an autoregulatory role for NLR activation and has been implicated in ligand sensing; however, the mechanism and ligands involved in this interaction remain unknown. The N-terminal domain is either a caspase-recruitment domain, pyrin domain or baculovirus IAP repeat domain; the individual domain dictates to which NLR subfamily a receptor belongs and the domain recruits adaptor and effector proteins to the NLR to drive downstream signal transduction.

Apparently, T cell-reactivity depends on HLA-restriction of the UTY-peptides which might be due to differential tissue-distribution of tissue-specific splice-variants. In dogs,

splice-variants CCI-779 molecular weight might also exist and be differentially expressed in organs/cell-types. Another possibility to identify UTY-tissue-distribution is to test UTY-specific CTLs in a skin-explant-model [52]. In any case only transplantation and adoptive immunotherapy will give answers regarding GvHD and conversion of chimerism after transfusion of UTY-specific CTLs obtained from immunized female donors or generated in vitro using autologous-DCs + peptides [53]. During our dog-UTY-studies, canine-Y-chromosome-/UTY sequence was not available in database (canine-genome data rose from female-dog material), but finally the dog-UTY this website sequence

was published [54]. Blast-analysis of canine-UTY- and human-UTY-protein-/peptide sequences including their corresponding X-chromosomal counterparts (UTX) was used to confirm the postulated UTY-analogies. Amino acid (AA) differences were present for W248 (AA6 + 9) and T368 (AA4 + 8) in the canine-sequence but substituted AAs bear comparable chemical properties (exception: T368-AA9: human: F-polar; dog: Y-unpolar), therefore showing high similarity. K1234-peptide sequence and UTY-homologue UTX sequences for all three peptides were identical in dogs. These alterations can also explain the different recognition-patterns of the three peptides in the context of the different dogs’ DLA-genotypes producing UTY-specific T cell reactivity or not (#1, #4, #6 versus #2, #3, #5, #7–#15). Therefore, the supposed similarities of canine- and human-UTY sequences were evidently proved by dog-UTY sequence explaining binding of human-peptides to canine-DLA [32]. Despite the use of the cUTY-sequence in Progesterone our experiments,

we could clearly demonstrate the generation of specific male- and MHC-I-restricted cCTL-reactivity evidently verifying UTY-expression, presentation and immunogenicity in dogs, although we cannot show data with the native canine-UTY peptides. As canine-sequences are expected to be highly homologous to their human orthologues, further scientific strategies have to focus on the amplification and sequence of the relevant canine cDNA-sequences using human-, mouse- and rat-UTY-sequences, resulting in the use of completely authentic canine-minor-epitopes. Indeed, BLAST-sequence alignments of dog-UTY with human-, mouse- and rat-UTY DNA, mRNA and protein revealed accordance in 89% for humans, 86% and 84% for mouse and rat, respectively.

Whether the dramatic loss of KU-60019 chemical structure circulating IL-17+CD4+ T cells results in IL-17 paucity in vivo is not known and may well be compensated by IL-17 produced by iNKT or γδ T cells 47. On-going studies aim to elucidate the mechanisms of increased effector cell sensitivity to Treg-cell mediated suppression beyond IL-17 expression and whether contact-dependent suppression noted in control cultures (Supporting Information Fig. 6) is also preserved in cells form HIV+ subjects. Our data on the loss of both Treg-cell and IL-17+ subsets extend other observations 18–25, 48. Both Treg-cell and IL-17 numbers correlate

with CD4+ T-cell numbers, indicating that these cells are lost as part of the overall decline in CD4+ T-cell count (Fig. 5). Whether the greater loss of IL-17 cells in progressors (Fig. 5C) 19 is indicative of these cells being preferentially targeted over and above Treg cells

by HIV 22, 49 or relates to other indirect mechanisms remains to be elucidated. Interestingly, HAART clearly restores effector CD4+ T-cell proliferative capacity (Fig. 1A), but not Treg or IL-17 cell numbers (Fig. 5). Kolte et al. 16 reported increased Treg-cell numbers 5 years after HAART initiation. However, similar to our study, Gaardbo et al. 17 report that Treg cell absolute numbers are significantly reduced prior to HAART, and remain the same at 24 wk following Decitabine datasheet therapy. The failure to restore Treg and IL-17 numbers may reflect inefficient CD4+ T-cell recovery despite efficient virus load control or relate to selective recovery of some but not all CD4+ T-cell subsets following antiviral therapy 50, 51. In conclusion, our data support the contention that Treg-cell function is preserved despite a significant decline in number across all groups

of chronic HIV subjects tested and that effector cells from chronic asymptomatic Cytidine deaminase HIV+ subjects, but not untreated progressors, are rendered more sensitive to suppression relative to controls. Our contention is that elevated sensitivity of effector to Treg-cell suppression may compensate for a reduction in Treg-cell number and reflect a natural host response in the chronic phase of HIV infection that is lost as patients’ progress to disease. A reduction in Treg-cell number with no compensatory increase in effector cell sensitivity to Treg-cell suppression would effectively reduce the net homeostatic control exerted by Treg cells. In turn this may contribute to T-cell activation, which is a hallmark of disease progression 30, 52, 53, thereby impacting HIV pathogenesis. Subjects were volunteers with HIV infection who attended the outpatient clinic at St Thomas’ Hospital, London. A total of 33 treatment naive HIV+ progressors were examined (Supporting Information Table 1).

The development and quality of the humoral immune response is to a large extent influenced by the immunological environment of the responding B cell. An expanding body of literature Lenvatinib nmr indicates that IFN-α contributes to shaping the adaptive immune responses47,48 and that direct type I IFN-mediated B-cell activation significantly

affects the quality and magnitude of the antiviral humoral responses.6–9 We and others previously reported that human pDCs, via their secretion of IFN-α, enhance B-cell responses induced by TLR ligation and/or T helper cell stimulation in vitro.1–4 Compared with mDCs, pDCs have shown less efficiency in presenting antigens to naive T cells and induce cellular immune responses.25,34 However, an increased understanding of the contribution of pDCs in shaping B cell responses is needed, especially with regard to vaccine-induced responses as antibodies are known to provide the protective effect

of most successful vaccines. To this end, central questions concern whether pDCs should be specifically targeted and activated by vaccine components. In the last decade, the clinical utility of TLR ligands as vaccine adjuvants and immune stimulatory therapies has evolved as an intensive area of investigation.10,12 Selected TLR ligands are under evaluation for their adjuvant effect both in non-human primate studies18–20 and https://www.selleckchem.com/products/Metformin-hydrochloride(Glucophage).html in human trials21–23 with promising results. As rhesus macaques to a large extent express similar repertoires of TLRs on immune cells

as humans do,26 they represent an indispensible in vivo model for testing of TLR ligands. In this study, we found that proliferation of human and rhesus B cells was induced by ligands targeting TLR7/8 and 9 but not TLR3. The different CpG classes, all binding TLR9, are well characterized on human cells in vitro2,32 and to some extent in vitro and in vivo in rhesus macaques.11,40,43,49 We found that CpG B Carnitine dehydrogenase was superior to CpG C at inducing proliferation in human B cells and this effect was inverted for rhesus B cells, which is consistent with previous reports.2,43 CpG B was originally identified to be a particularly potent stimulus of human B cells.50,51 There may be differences in CpG recognition mechanisms among primates making CpG C more efficient in the rhesus system. CpG A, in contrast, induces high amounts of type I IFN from pDCs2,32,40 because of its palindromic CpG phosphodiester sequences with phosphorothioate G-rich ends. The phosphorothioate CpG C with a stimulatory CpG and a palindromic sequence at the 5′ or 3′ end combines the effects of CpG A and CpG B32,52 and may exhibit fewer species-specific features. Regardless of stimuli, a higher level of proliferation was observed for human B cells compared with rhesus B cells by TLR ligand stimulation.

We thank Professor Caroline Sabin and Doctor Pedro Coutinho for support in statistical analysis. We are also grateful to all the blood donors who took part Panobinostat mouse in this study. The authors declare no financial conflicts of interest. Figure S1. High frequency

of cytomegalovirus (CMV) – specific CD4+ T cells. Peripheral blood mononuclear cells were stimulated with CMV, Epstein–Barr virus (EBV), herpes simplex virus (HSV), varicella zoster virus (VZV) or purified protein derivative (PPD) lysate and the percentage of interferon-γ (IFN-γ) secreting antigen-specific CD4+ T cells was assessed by flow cytometry (a). The frequency of CD4+ T cells that were specific for CMV, EBV, HSV, VZV or PPD was determined in individuals who were seropositive for these agents (b). Only responses >0.02% above background (unstimulated cells) were considered positive. Horizontal lines depict median values. Significantly increased frequency of CMV specific CD4+ T cells relative to the other antigens is indicated (Wilcoxon rank test, GraphPad Prism). Figure S2. Multiparameter flow cytometric analysis. Kinase Inhibitor Library high throughput Representative dot plots from

one donor show the distribution of stimulated CD4 T cells within each CD45RA/CD27 subset. Panels show CD4 plotted against: CD40 ligand (CD40L; upper right), interferon-γ (IFN-γ; upper left), interleukin-2 (IL-2; lower right) and tumour necrosis factor-α (TNF-α; lower left), each for unstimulated and anti-CD3 stimulated T cells. Figure S3. Cell recovery. Purified CD45RA/CD27 CD4+ T-cell subsets were activated with anti-CD3

and irradiated antigen-presenting cells and irradiated antigen-presenting cells. At the indicated time-points, the cell number was determined on a haemocytometer. Results are expressed as a percentage of the initial number of cells placed in culture; results for one donor are shown. (b,c) Apoptosis was assessed by Annexin V staining and propidium iodide (PI) incorporation. The percentage of early apoptotic (Annexin V+ PI–) and late apoptotic/necrotic (Annexin V+ PI+) cells was assessed in the indicated days. Representative pseudocolour plots are 3-oxoacyl-(acyl-carrier-protein) reductase shown (b). Figure S4. CD4+ CD45RA– CD27+ cells were purified by FACS sorting and analysed for the expression of CD45RA and CD45RO before culture. Cells were stimulated with interleukin-2 (IL-2) or IL-15 and CD45RA/CD45RO expression was assessed by flow cytometry at the indicated time-points. The results shown are representative of four experiments. Figure S5. CD4+ CD45RA– CD27– cells were purified by FACS sorting and analysed for the expression of CD45RA and CD45RO before culture. Cells were stimulated with interleukin-7 (IL-7), IL-2 or IL-15 and CD45RA/CD45RO expression was assessed by flow cytometry at the indicated time-points. The results shown are representative of three experiments. Figure S6. CD4+ CD45RA– CD27+ cells were purified by FACS sorting.

Helicobacter pylori is able to transform to a coccoid form, which is able to access the intestinal lumen and is subsequently captured by DC in Peyer’s patches (PP) (Nagai et al., 2007). The CD4-positive T cells that are activated PLX4032 in PP subsequently migrate into the gastric mucosa, resulting in the development of gastritis (Kiriya et al., 2007; Nagai et al., 2007). In the inflammatory response, T helper (Th) 1 and Th2 lymphocyte-derived cytokines

control the clearance of intracellular and extracellular pathogens, respectively. According to this Th paradigm, the T cells in the H. pylori-infected gastric mucosa are predominantly Th1 cells, which secrete interferon (IFN)-γ (D’Elios et al., 1997; Bamford et al., 1998; Itoh et al., 1999), and H. pylori infection leads to the upregulation of IFN-γ production and the downregulation of interleukin (IL)-4 and IL-10 production in the gastric mucosa, resulting in the enhancement of the Th1 pathway and the subsequent development of chronic gastritis (Smythies et al., 2000). Th17 cells, which produce IL-17, modulate the Th1 response in gastric inflammation induced by H. pylori (Kabir, 2011). In addition, the role of regulatory T cells in H. pylori infection is now being investigated regarding escape from the host immune response (Kandulski

et al., 2010). Thus, the role of CD4-positive T cells has been widely studied in the context of adaptive immunity against H. pylori. On the contrary, immune responses against H. suis and the relationship between H. suis and gastric disease have been less Torin 1 purchase understood. Recently, Nakamura et al. (2007) reported the animal model of gastric Reverse transcriptase MALT lymphoma using H. suis, previously named ‘H. heilmannii’ type 1, obtained from a Cynomolgus monkey. In this model, the formation of MALT lymphoma-like lesions was observed in 100% of mice at 6 months after infection. In our previous study using the same animal model, the mRNA expression level

of IFN-γ was upregulated in the gastric mucosa of C57BL/6J mice at 3 months after H. suis inoculation, suggesting the occurrence of a local Th1 response (Nobutani et al., 2010). However, regarding H. suis infection, no detailed analysis of cytokine profiles or experiments using cytokine-deficient mice have been performed. In the present study, we aimed to assess the role of helper T cells in the development of gastric lymphoid follicles in H. suis-infected animals. C57BL/6J wild type (WT), IFN-γ−/−, and IL-4−/− mice were infected with H. suis, and then histological and immunohistological examinations were carried out. In addition, the expression levels of Th cytokines in the gastric mucosa of C57BL/6 WT mice were examined. All animal experiments were performed according to the ‘Guidelines for Animal Experimentation at Kobe University (Permission No. P-090707)’. C57BL/6J WT mice were purchased from CLEA Japan Inc. (Shizuoka, Japan). IFN-γ−/− mice (Tagawa et al.

The individual

parameters were scored from 1 to 3, and a cumulative score between 0 and 19 was recorded for each biopsy. The observer was blinded (J.H.E). Values are expressed as the mean ± 2 SD. To compare the treatment group with controls, we used the Mann–Whitney U-test. To evaluate the differences between before treatment, during and after treatment, the normality of each type of measurement was evaluated using a KS test based on the residuals from a simple linear model using patient and time as factors. In no case was normality close to being rejected (P > 0.4 in all cases). Hence, one-way repeated-measures anova was used. However, to evaluate the differences between the two treatment groups, two-way repeated-measures anova was used. Three patients who received combined treatment were not evaluated at week 8 because they had started another psoriasis Pifithrin-�� molecular weight treatment due to exacerbations: two of those patients at week 4 (Fig. 1A; BL3 and BL6) and one patient at week 7 (Fig. 1A; BL1). For these patients, PASI find more evaluation was made at the time point their study participation was terminated, and they were not included

in the analysis at week 8. All measurements were taken using sigmastat 3.1 (Systat Software, San Jose, CA, USA). A P-value ≤ 0.05 was considered statistically significant. In order to evaluate whether clinical improvement of psoriasis following bathing in geothermal seawater combined with NB-UVB and NB-UVB alone is preceded by changes in systemic inflammatory markers, the clinical efficacy of each treatment regimen was evaluated first. As shown in Fig. 1C, both treatment regimens demonstrated significant clinical improvements. Furthermore, the data suggested that patients receiving combined treatment Sirolimus demonstrated better clinical response, measured by the PASI score, than patients treated only with NB-UVB. This was seen both

after one week (% improvement: combined treatment 37.3 ± 10.3 versus NB-UVB treatment 18.3 ± 8.9, P < 0.05) and after three weeks (67.3 ± 11.9 versus 22.0 ± 12.0, P < 0.0001). However, this was not the main aim of the study, and larger cohort and another control group would be needed to fully address this interesting observation. Interestingly, bathing in the Blue Lagoon immediately following skin punch biopsy resulted in no infections and only minor skin irritation resolving in few days. In addition, the above clinical findings were confirmed by the histological Trozak’s score where patients in both treatment groups showed a significant histological improvement at week 3 (Trozak’s score: BL treatment = 10.3 ± 5.5 versus NB-UVB treatment = 8.0 ± 4.6; Fig. 2).