It is conceivable that our RTL constructs are representative of naturally occurring Selleckchem PS341 soluble two-domain MHC-II structures that may function as inhibitors of T-cell responses. In our recent phase I safety study of RTL1000

in DR2+ MS subjects discussed above, we observed detectable pre-infusion plasma levels of two-domain RTL-like structure in 4 of 13 donors (31%). To verify these intriguing results, we re-evaluated pre- and post-infusion serum or plasma samples from six MS subjects from our trial and serum from a pool of three healthy donors using the 1B11 Fab specific for two-domain MHC-II structures (with no specificity for bound peptide). Diverse quantities of such structures (ranging from 13 to 1038 ng/mL) were found in all evaluated subjects.

These novel results suggest the natural occurrence of two-domain structures that could be derived from four-domain intermediates possibly shed from MHC-II expressing APC upon immunization 42. The conformational sensitivity of Fab 1B11 for the distinct RTL shape implies that such native MHC-II-derived structures carry an RTL-like conformation and therefore may act as natural analogues of RTL constructs and induce similar regulatory effects on T-cell responses. Most importantly, the appearance of natural two-domain MHC-II molecules in human plasma would provide support for selleck chemical the biological relevance of our RTL constructs. Our Abs directed to the two-domain MHC conformation are valuable tools for isolation and identification

of such native structures. The comparison between the signal levels detected by Fab 1B11 (pan DR two-domain structures) and Fab 2E4 (DR2–MOG-35-55 two-domain structure of RTL1000) in the plasma of subjects after infusion of RTL1000 demonstrates the Carnitine palmitoyltransferase II high sensitivity of our Fabs. We are currently in the process of increasing the avidity of 1B11 Fab by expressing it as whole IgG, which will allow us to immunoprecipitate and further study such novel serum structures. In PK studies of our clinical trial discussed above we observed a short half-life (∼5 min) of circulating RTL1000 post infusion 34. For the detection of RTL1000 in plasma and serum samples of the subjects, we used polyclonal Abs in sera from mice immunized with RTL1000. The high specificity of Fab 2E4 to RTL1000 in a peptide-restricted manner enabled its sensitive detection of circulating RTL1000 in plasma samples with no background of native MHC and other-peptide specificities of RTL-like structures. Using Fab 2E4 we developed a new assay for PK studies and measurement of RTL1000 levels in serum. This assay was found to have greater sensitivity (∼two-fold) compared to the use of polyclonal serum Abs in the original assay and therefore allows more accurate PK studies (manuscript in preparation). The therapeutic effects of RTLs on T-cell-mediated autoimmunity may involve several complementary pathways.

To date, five subtypes of muscarinic Regorafenib acetylcholine receptors (M1R–M5R) have been identified, and M3R is expressed in exocrine glands and plays crucial roles in exocrine secretion. Acetylcholine

binds to and activates M3R on salivary gland cells, causing a rise in intracellular Ca2+ via inositol 1, 4, 5-trisphosphate (IP3) and IP3 receptors. Consequently, the rise in intracellular Ca2+ activates apical membrane Cl– channels and induces salivary secretion [1]. Activation of M3R also induces trafficking of aquaporin 5 (AQP5) to the apical membrane from the cytoplasm, which causes rapid transport of water across the cell membrane [2]. M3R has four extracellular domains: the N-terminal region and the first, second and third extracellular Vorinostat clinical trial loops. Among these domains, the second extracellular loop is critical for receptor activation by agonists [3]. Therefore, the second extracellular loop of M3R has been the focus of our interest, and we report a subgroup of SS patients who had anti-M3R antibodies that recognized the second extracellular loop of M3R [4,5]. Although these data indicate that the second extracellular loop is the target

antigen, the precise epitopes are currently unknown. A recent study reported that the third extracellular loop represents a functional epitope bound by IgG derived from SS patients [6]. The present study was designed to clarify the precise B cell epitopes of M3R and the function of anti-M3R antibodies. For this purpose, we screened sera of SS patients for anti-M3R autoantibodies against all four extracellular domains of M3R by enzyme-linked immunosorbent assay (ELISA) using synthetic peptide antigens and performed functional assays of these antibodies using human salivary gland (HSG) cells. We assessed the correlation between epitopes and function and various clinical features. Serum samples were collected from 42 Japanese patients with SS (15 with primary SS and 27 with secondary SS) who had been followed-up at the Division of Rheumatology, University of Tsukuba Hospital, Ibaraki, Japan. All patients with SS satisfied selleck products the Japanese

Ministry of Health criteria for the diagnosis of SS. These criteria included four clinicopathological findings: lymphocytic infiltration of the salivary or lacrimal glands, dysfunction of salivary secretion, keratoconjunctivitis sicca and presence of anti-SS-A or SS-B antibodies. The diagnosis of SS was based on the presence of two or more of the above items. We also recruited 42 healthy controls (HC). Approval for this study was obtained from the local ethics committee and signed informed consent was obtained from each subject. We synthesized different peptides encoding the extracellular domains of human-M3R. The N-terminal of human-M3R has a 66-mer amino acid sequence, and accordingly we divided this domain into three segments.

Three of the five positive patients are common to both studies; we identified an additional two APS1 patients find protocol – one male patient and one female patient with autoantibodies against TSGA10. In contrast to the previous study, we also detected TSGA10 autoantibodies in five patients with SLE of which one had high-titre autoantibodies, and also at low titre in a single healthy blood donor. Furthermore, TSGA10 autoantibodies

were found to be present from a very young age in the majority of APS1 patients testing positive and once the patient has seroconverted, TSGA10 autoantibody titres remained fairly consistent for each patient over the duration of the disease. TSGA10 is highly expressed in the testis [21] where it is processed to form a structural protein of the fibrous sheath in mature spermatozoa [22]. No expression of TSGA10 mRNA was detected in the testes of two infertile men [21] suggesting a link between TSGA10 and infertility. Primary ovarian failure develops DAPT supplier in approximately 65% of female APS1 patients, whereas male hypogonadism is far less common, appearing in one fourth of male patients [23]. Of the five TSGA10 autoantibody-positive APS1 patients, the four male patients were not diagnosed with hypogonadism, but

the one positive female patient had primary ovarian failure. None of the remaining 34 patients with gonadal failure had detectable TSGA10 autoantibodies, suggesting that this antigen does not function as a gonadal antigen in APS1 patients. Likewise, none of the five TSGA10 autoantibody-positive SLE patients suffered from any fertility problems, further signifying TSGA10 is not functioning as a gonadal antigen in these patients. TSGA10 mRNA, while found at high levels in the testis, has also been shown to be almost ubiquitously expressed throughout the body, albeit at much lower quantities [24]. We have also confirmed these results and further shown TSGA10 mRNA to be moderately expressed in the pituitary gland and aorta, with very little expression in the adrenal

cortex. It has been previously proposed that the function of TSGA10 may not just be limited to spermatogenesis but have a more widespread role throughout the body Reverse transcriptase being expressed in actively dividing or post-mitotic cells [25]. The finding of TSGA10 mRNA being expressed in many organs helps support this hypothesis. Its antigenic target in APS1 may therefore be in any organ where expression is seen. We isolated TSGA10 from a pituitary cDNA library and showed moderate levels of mRNA expression in this organ. Therefore, we investigated TSGA10 as a potential pituitary antigen. No association however, was observed between TSGA10 autoantibody status and pituitary manifestations in APS1, with the protein being isolated from a patient with no pituitary defects and none of the other positive patients diagnosed with a pituitary deficit.

This last phenomenon was also observed when twofold, fourfold or eightfold lower concentrations of blocking peptides against pNF-κB p65 or pSTAT3 were used (data not shown). To assess the roles of NF-κB p65 and STAT3 in the later processes of cell differentiation (i.e. the final production of Ig), we sought to stimulate purified blood B cells with sCD40L + IL-10 while simultaneously blocking either one or both of the

transcription pathways using specific blocking peptides against pNF-κB p65 or pSTAT3. The pNF-κB p65 blocking peptide led to a modest, but significant, 20% decrease in pNF-κB p65. The anti-pSTAT3 peptide alone had nearly the same effect, resulting in an 18% reduction in pNF-κB p65. Together, the blocking peptides against pNF-κB p65 and pSTAT3 reduced NF-κB p65 phosphorylation Selleck FK228 Selleckchem Proteasome inhibitor by 28% (Fig. 8b). Reciprocally, the anti-pSTAT3 peptide significantly reduced pSTAT3 by 45% (Fig. 8c), while the anti-pNF-κB p65 peptide reduced it by 30%. Combined, these blocking peptides reduced pSTAT3 by 73%. IgA production was completely inhibited; however, phosphorylation of NF-κB and STAT3 was not blocked completely. These observations were probably due to neo-phosphorylation induced by other stimuli or by the oscillations in NF-κB signalling, as could have been

expected [32]. These data indicate that there is probably co-operation between Amylase the various transcription factor pathways, and in particular, an NF-κB influence on the STAT3 pathway. Furthermore, these results suggest that sCD40L acts first on purified B cells, promptly activating the classical NF-κB pathway and inducing IL-10R expression (experiments and data not shown), which then renders the STAT3 pathway reactive to IL-10 signalling. We aimed

to elucidate some of the molecular pathways involved in providing purified B lymphocytes with the differentiation signals of non-cognate T cell surrogates, i.e. the classical sCD40L/CD40 + IL-10/IL-10R signals, leading to the skewed production of Ig towards IgA. We deliberately excluded from this investigation the addition of exogenous TGF-β, described classically as an IgA differentiation factor in a number of studies, on the basis of preliminary experiments (Fig. 2a and data not shown), having shown that TGF-β antagonized the differentiating role of sCD40L and IL-10 towards IgA class switch in this culture system. However, because these experiments were performed initially by culturing purified B lymphocytes in FCS-containing medium, the possibility that TGF-β eventually present in this serum may have biased our results was considered, as has been described, e.g. for the plasticity of T helper 17 (Th17) responses [33]. TGF-β1 induces IgA switching and secretion in stimulated B lymphocytes in mouse spleen. This has also been shown for IgG2b using mouse spleen B cells.

We compared the 7-year all-cause and cardiovascular mortality of the subjects with albuminuria (albumin-creatinine ratio ≥ 30 mg/gCr), proteinuria (≥ ±) and (≥ 1+) by dipstick. Results: The prevalence of the subjects with albuminuria, proteinuria (≥ ±) and (≥ 1+) were 14.9%, 8.4% and 4.4%, respectively. During the follow-up period (median 6.4 years), the all-cause and cardiovascular Raf inhibitor mortality was 4.0% (138 subjects) and 1.2% (41 subjects), respectively in the total population. In Kaplan-Meier analysis, the all-cause mortality of the subjects with albuminuria (7.4%), proteinuria (≥ ±) (7.2%) and (≥ 1+) (9.3%) were significantly higher than those of the counterparts without urinary

abnormality. In Cox-proportional analyses with the adjustment for possible confounders, albuminuria, but not dipstick proteinuria was an independent learn more factor for the all-cause and cardiovascular mortality. In subgroup analyses, the hazard ratio of albuminuria was high, especially in the diabetic and non-hypertensive population. Conclusion: Albuminuria showed a higher

predictive ability for the all-cause and cardiovascular mortality than dipstick proteinuria in the Japanese community-based population. MATHEWS SHARON, T1, VIJAYAN MADHUSUDAN2, VEERAPPAN ILANGOVAN1, REVATHY LAKSHMI2,3, T THYAGARAJAN2, MATHEW MILLY1,2,3, ABRAHAM GEORGI1,2,3 1Pondicherry Institute Of Medical Sciences; 2Madras Medical Mission; 3Tanker Introduction: Hydration

and nutritional status of end stage renal disease(ESRD) patients are linked to increased morbidity and mortality. Body composition monitoring (BCM) by Multi frequency Bioimpedance spectroscopy (MFBS) is considered to be a superior modality of fluid assessment in CKD–Dialysis. Carbohydrate We did a longitudinal prospective study in south India on maintenance haemodialysis(MHD) and continuous ambulatory peritoneal dialysis(CAPD) patients over 24 months and looked at impact of baseline nutritional parameters and body composition parameters on 24 month mortality. Methods: Ninety nine patients stable on dialysis for at least 3 months were recruited (MHD 85, CAPD 14) at baseline and at 24 months, 41 were alive and 33 died, 12 underwent renal transplant and 13 were lost to follow up. BCM and nutritional assessment were done at baseline and at follow up. Results: Baseline overhydration differed significantly between surviving and dead patients (p < 0.05). Receiver operating characteristic(ROC) curve between overhydration and mortality showed area under the curve was >50% with best cut-off point to predict mortality as 3.15 L. ROC curve for BMI showed cut off of 22.65 kg/m2 to predict mortality, with sensitivity 41.30 % and specificity 81.81 %. At follow up, triceps skin fold thickness(TSF), biceps skin fold thickness(BSF) and mid arm circumference(MAC) increased significantly from baseline (p < 0.001, p= 0.001 and p.

Clostridium septicum is a gram-positive, spore-forming anaerobe that causes

a variety of disease syndromes in humans and animals [1, 2]. This organism produces several extracellular factors, including deoxyribonuclease, hyaluronidase, neuraminidase and alpha-toxin [3]. Alpha-toxin, the major virulent factor, has hemolytic, lethal and necrotizing activities [4, 5]. Alpha-toxin is a pore-forming toxin that belongs to the same family as aerolysin from Aeromonas hydrophila [6] and epsilon-toxin from Clostridium perfringens [7]. Alpha-toxin is secreted by the organism as an inactivated 46 kDa protoxin [8, 9]. The protoxin binds to GPI-anchored proteins on cell surfaces with high affinity [10, 11]. The protoxin is then cleaved to its 43 kDa active form by host cell proteases, such as furin [5, 8]. Activated toxin Fulvestrant concentration monomers interact with each other on DRMs to form oligomeric prepore complexes [12, 13]. The prepore complexes ultimately insert into the plasma membrane, generating pores that are approximately 1.3–1.6 nm in diameter [4, 8]. Alpha-toxin and aerolysin show structural and functional similarities, at the level of 72%, with 27% identity [6, 9]. Although GPI-anchored Akt inhibitor proteins also act as receptors for aerolysin, each toxin binds to different subsets of GPI-anchored proteins [10]. Furthermore, the most striking difference between

alpha-toxin and aerolysin is that D1 of aerolysin is missing from the amino terminus in alpha-toxin, implying that alpha-toxin is a single-lobed structure consisting of three domains, D1, D2, and D3, which are homologous to D2, D3, and D4 of aerolysin, respectively (Fig. 1) [6, 14, 15]. The functional domains and

amino acids of alpha-toxin involved in receptor binding, oligomerization and pore formation have been identified by Melton et al. [14, 16]. Binding of alpha-toxin to GPI-anchored proteins is restricted to D1 [16]. Because cholesterol is essential Anidulafungin (LY303366) to binding and stability on the cellular membrane for many kinds of pore-forming toxins from gram-positive bacteria, these toxins have been named CDCs. CDCs that bind specifically to membrane cholesterol, such as perfringolysin O [17], streptolysin O [18], pneumolysin [19] and listeriolysin O [20], have a region of 11 highly conserved amino acid residues, ECTGLAWEWWR (tryptophan-rich motif) that is located in the C-terminal region of each toxin. In perfringolysin O, three tryptophan residues in the tryptophan-rich motif have an important role in binding to the cell membrane [21]. Although C. septicum alpha-toxin does not bind to cholesterol but to GPI-anchored proteins on the cell surface, alpha-toxin also has a tryptophan-rich region lying within an 11 amino acid sequence in D1 near the C terminus (NGYSEWDWKWV; residues 302–312; Fig. 1) [6]. In a previous study, Melton-Witt et al.

LC exposure to VIP or PACAP enhanced IL-6 production upon Ag presentation to responsive CD4+ T cells (Fig. 4A). We then set up similar experiments in which anti-IL-6 mAb were added to Ag presentation cultures to neutralize this cytokine with isotype control mAb added to control wells. Addition of anti-IL-6 mAb significantly blocked the effects of VIP or PACAP on enhancement of IL-17A production (Fig. 4B). To determine whether VIP or PACAP can modulate the immune response in vivo, groups of BALB/c mice were injected intradermally with PACAP, VIP, or medium alone. Fifteen minutes later, mice were immunized by topical application of dinitrofluorobenzene (DNFB) at sites of injection.

Three Palbociclib mouse days later, draining lymph nodes were harvested and a single cell suspension of lymphocytes was stimulated in culture with anti-CD3 and anti-CD28. After 72 h, supernatants were assayed for cytokine

content. Lymphocytes from mice treated with PACAP or VIP produced significantly more IL-17A and IL-4 with significantly less IL-22 and IFN-γ compared with cells from control mice (Fig. 5). Among the skin’s protective properties are innate and adaptive immune functions to protect against environmental and microbiologic click here challenges [[45]]. Many observations suggest that the nervous system plays a role in regulating cutaneous immunity. Although definitive studies are difficult, it is generally believed that stress modulates inflammatory skin disorders including psoriasis, atopic dermatitis, and roasacea, among others [[46-48]]. Of particular interest, psoriasis has

been reported to clear from denervated sites [[49-51]], suggesting a role for the nervous system in that disorder. Both the LC-like cell line XS106 and primary murine LCs express mRNA for VPAC1 and VPAC2 receptors Tolmetin [[52]] and culture of LCs in VIP or PACAP inhibits their ability to present Ag for elicitation of delayed-type hypersensitivity in previously immunized mice [[15, 16]]. Also, intradermal administration of PACAP suppressed induction of contact hypersensitivity at the injected site [[15]]. PACAP and VIP inhibited the ability of LC to present Ag to a Th1 clone and augmented IL-10 production by a lipopolysaccharide (LPS)-stimulated LC-like dendritic cell line, while downregulating LPS-stimulated IL-1β and IL-12 p40 production [[15, 16]]. Our current observations, that PACAP or VIP treatment of LCs enhances the generation of Th17 cells and enhances IL-17A and IL-4 release while inhibiting IL-22 and IFN-γ production, support the hypothesis that neural activity regulates and directs immune function. Of course, LCs are not the only APCs in the skin; several dendritic cell subsets are present in murine skin that exhibit functional specialization [[53, 54]]. There is evidence that LCs are able to present Ag for the generation of Th17 cells [[54, 55]] while Langerin+ dermal DCs do not [[55]].

Developing means of selecting patients most likely to benefit from revascularization is vital. New imaging techniques and use of biomarkers are two avenues under active investigation. Concurrently, technical advances such as drug eluting stents and embolic protection

devices (EPD) need to be assessed. MR imaging can provide a multipurpose assessment during investigation of ARVD. ABT-263 nmr Detailed assessment of not just renal morphology, but also function can be acquired from a single MR study.64–67 Although routinely measured, renal bipolar length is a poor predictor of renal parencymal volume, and yet the latter is the best predictor of single kidney GFR.68 Recent studies have encouragingly shown that kidney volume to GFR ratios in RAS kidneys might predict those that will benefit from revascularization, presumably by identifying kidneys with well-preserved renal parenchyma and/or relatively rapidly developing RAS lesions.69 This builds on the concept of ‘hibernating parenchyma’, a term used to describe renal tissue which has not yet undergone permanent damage and which may benefit from restoration of blood flow via revascularization.70 An

alternative term is ‘functionally significant stenosis’– a disproportionately low GFR despite preserved parenchymal volume reflecting potentially reversible reduced renal plasma flow. In light of concern regarding NSF, non-gadolinium enhanced MR functional imaging is an Selleck KU-60019 avenue of expanding research. Methods which ‘label’ various components in the blood in an attempt to understand renal perfusion and function, for example, deoxyhaemoglobin (in blood oxygen level dependent imaging) and blood water flow (arterial spin labelling) are two such methods under investigation.71 Cell Penetrating Peptide There is also increasing interest in the value of biomarker analysis in patients with ARVD. Vascular endothelial growth factor (VEGF) is an endothelial-specific growth factor and within the kidney it is expressed by tubular epithelial cells and glomerular podocytes. Its most vital function is to stimulate capillary endothelial cell growth and proliferation, primarily

in response to hypoxia, but release is also triggered by platelet aggregation at endothelial surfaces in response to vascular injury.72 Loss of VEGF is associated with development of glomerulosclerosis and tubulo-interstitial fibrosis.73 Although VEGF is a biomarker for renal ischaemia associated with RAS, it may also have potential utility as a treatment – for example, it can preserve the microvascular circulation in pig models of RAS. In these studies, pigs with RAS infused with VEGF developed significantly less glomerulosclerosis and tubulo-intersitital fibrosis than those untreated, and treated kidneys looked structurally similar to non-RAS kidneys.74 Brain natriuretic peptide (BNP) is a neurohormone released from cardiac myocytes.

The authors declare no conflicts of interest. “
“It has been proposed that mannose-binding IDH phosphorylation lectin (MBL) levels may impact

upon host susceptibility to tuberculosis (TB) infection; however, evidence to date has been conflicting. We performed a literature review and meta-analysis of 17 human trials considering the effect of MBL2 genotype and/or MBL levels and TB infection. No significant association was demonstrated between MBL2 genotype and pulmonary TB infection. However, the majority of studies did not report MBL2 haplotype inclusive of promoter polymorphisms. Serum MBL levels were shown to be consistently elevated in the setting of TB infection. While this may indicate that high MBL levels protect against infection with TB, the increase was also of a degree consistent with the acute-phase reaction. This analysis suggests that the relatively poorly characterized MBL2 genotypes reported are not associated significantly with susceptibility to pulmonary TB infection, but high MBL serum levels may be. Balanced polymorphisms

are the result of beneficial effects of resistance to prevalent infections due to physiological changes consequent on genetic variation. Well-characterized examples in human biology include haemoglobinopathies (sickle-cell and alpha-thalassaemia) and Plasmodium falciparum[1]. One of the most common polymorphisms on a global scale is that involving mannose-binding lectin (MBL), a pattern recognition receptor of the innate immune system. This liver-derived, acute-phase reactant recognizes pathogen-associated molecular patterns, Ibrutinib mw Glycogen branching enzyme killing microorganisms via activation of the lectin complement pathway and opsonophagocytosis [2,3]. MBL is also involved

in modulation of other inflammatory pathways contributing to autoimmune disease, apoptosis and vascular disease [4]. Despite its manifold effects in innate immune system pathways, there is a high frequency of MBL deficiency that arises due to polymorphisms of the MBL2 gene. The evolutionary advantage of MBL deficiency is unclear. MBL production is controlled by the MBL2 gene, and polymorphisms of the structural regions of the gene or its promoter are associated with relative or absolute serum MBL deficiencies [5]. The presence of key structural and promoter polymorphisms in a detailed MBL2 haplotype is reasonably well correlated with reduced serum MBL levels, and genotypic analyses are used frequently as surrogates for MBL serum levels. The MBL2 structural gene variants, B, C and D, are referred to collectively as O while A is the wild-type. Prior to recognition of the importance of MBL2 promoter polymorphism, MBL deficiency was defined on the basis of structural gene polymorphism alone and variably as the presence of any variant allele, [AO or OO] or compound heterozygosity for variant alleles [OO].

Using immunohistochemical staining, we found no difference in cell infiltration between healthy skin and skin from challenge sites of non-responders after 48 h, indicating that the lack of response was not due to active down-regulation. In agreement with this, we did not find any significant up- or

down-regulation of gene expression in the challenge sites of non-responders after 48 h. Furthermore, mRNA expression in elicitation responses of patients with psoriasis and healthy controls could not be distinguished, either in the positive or negative reactions, indicating that the clinical selleck chemicals llc difference between the groups is not due to a difference in down-regulation at the elicitation site. Regulatory T cells have been found to be dysfunctional in suppressing auto-antigen specific effector T cells in various autoimmune diseases [22–25], but their regulation of environmental antigens were not investigated in these studies. It is theoretically possible that some sort of down-regulatory event took place before 48 h at which the biopsy was taken; however, a cellular response would be expected to be present at this time-point. The significance of a T helper type 17 (Th17) profile in

autoimmune diseases is well established through multiple areas of research, as reviewed by Steinmann [26], and patients with autoimmune diseases have Epacadostat been demonstrated to have higher than normal levels of circulating Th17 cells and cytokines such as interleukin (IL)-17, IL-6, IL-21, IL-22 and IL-23 [27]. We hypothesize that the highly Th17-directed cytokine milieu in patients with autoimmune diseases interferes with the mounting of a contact allergic response. This could be due to interference in the differentiation of naive T cells to become effector or memory T cells necessary for the contact allergic reaction or to regulation of antigen-presenting cells. Interestingly, in a murine study, Brandt et al. demonstrated that short-term incubation of in vitro-generated dendritic cells C-X-C chemokine receptor type 7 (CXCR-7) (DC) with IL-21 significantly reduced their potential to induce an antigen-specific CD8+ T cell proliferation [28,29].

Antigen-presenting cells, particularly Langerhans cells, play a pivotal role in the sensitization phase of contact allergy, as they are responsible for the processing, transport and presentation of allergens to naive T lymphocytes in the skin, draining lymph nodes. Cumberbatch et al. found that the function of epidermal Langerhans cells, specifically Langerhans cells mobilization and migration, is profoundly impaired in the uninvolved skin of psoriasis patients compared with the skin of healthy volunteers [30]. The authors hypothesized that this could be due to disease progression characterized by systemic changes that affect Langerhans cell function. The systemic changes could be due to a Th17-skewed milieu found not only in psoriasis patients, but also in patients with other autoimmune diseases.