Kif26a KO buy GW-572016 and HET mice are useful animal model of oligonephronia and secondary FSGS. Kif26a may be one of resposible genes for familial oligonephronia. SAIPRASERTKIT NALINEE1, KATAVETIN PISUT2, CHUENGSAMAN PIYATIDA3, SUANKRATAY CHUSANA4, KANJANABUCH TALERNGSAK2, EIAM-ONG SOMCHAI2, TUNGSANGA KRIANG2, THAILAND PERITONITIS STUDY GROUP* 1Division of Nephrology, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand; 2Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University,

Bangkok, Thailand; 3Banphaeo Hospital (Public Organization), Bangkok, Thailand; 4Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Introduction: Treatment of peritoneal dialysis (PD)-related gram-negative bacterial peritonitis with single antibiotic regimen according to anti-microbial susceptibility does not always yield a satisfactory outcome. Recently, the use of combined antibiotics in peritoneal dialysis-related peritonitis caused by gram-negative bacteria has been reported to have better outcome compared with single therapy in retrospective studies. However, there was no randomized small molecule library screening controlled study directly comparing these two regimens. Methods: A multicenter, randomized controlled study was conducted in 22 PD centers throughout the

nation over a 12-month period. After the anti-microbial susceptibility testing was determined, the community acquired PD-related gram-negative bacterial peritonitis patients were randomized to receive either single antibiotic or two synergistic antibiotics. The primary endpoint was a composite clinical outcome,

including failure of treatment, re-infection (relapsing, recurrent and repeat peritonitis), and patient death. Results: One hundred and three patients with gram-negative PD-related peritonitis were enrolled to this study. Fifty-two patients were randomized to single antibiotic group while 51 patients were randomized to double antibiotics group. Both groups had similar baseline IKBKE characteristics. The primary composite endpoint of single and double antibiotics group were similar (25.5 versus 25.0%, p = 0.96). There were also no difference in complete cure rate (88.5 versus 92.2%, p = 0.53), re-infection (relapsing, recurrent and repeat peritonitis) (17.9 versus 21.0%, p = 0.78) and death (12.9 versus 18.5%, p = 0.73) between both groups (single versus double). No antibiotic-associated adverse events were reported. Conclusions: Combined antibiotics did not provide additional benefits over single effective antibiotic in community-acquired PD-related gram-negative bacterial peritonitis. Therefore, treatment with two synergistic antibiotics should not be routinely prescribed in Thailand until there is more available supporting evidence. (ClinicalTrials.gov number, NCT01785641.

The protein concentrations in the cytoplasmic fraction and nuclear fraction were quantified

by BCA protein assay kit (Thermo Fisher Scientific) according to the manufacturer’s instructions. The proteins were denatured with 4× sample loading buffer (100 mm Tris–HCl, pH 6·8, 200 mm dithiothreitol, 4% SDS, 20% glycerol and 0·2% bromophenol blue) at 95° for 5 min. Equal amounts of proteins were resolved in 10% SDS–PAGE and then transferred onto nitrocellulose membrane (Whatman, Maidstone, UK). The membranes were blocked and then incubated with primary antibodies against iNOS, phospho-JNK, JNK, phospho-p38 MAPK, p38 MAPK, phospho-ERK1/2, Belnacasan ERK, IκBα, NF-κB p65, actin or lamin B overnight at 4°, followed by incubation with corresponding HRP-conjugated secondary antibodies for 1 hr. The protein bands were visualized using enhanced chemiluminescence solutions (GE Healthcare, Little Chalfont, see more UK). Statistical analysis was assisted by GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA). Student’s t-test or one-way analysis of variance with Newman–Keuls post-hoc test was adopted when appropriate. P < 0·05 was considered

statistically significant. To investigate whether IL-17A affects NO production in BCG-infected macrophages, we first investigated the effects of various doses of IL-17A on BCG-induced NO production in human MDM. The macrophages were pre-treated 17-DMAG (Alvespimycin) HCl with recombinant human IL-17A at 5, 25 or 100 ng/ml for 24 hr, followed by BCG infection for

24–72 hr. We observed that human MDM failed to produce substantial amounts of NO in response to BCG infection. The level of NO in BCG-infected macrophages was comparable to that in untreated cells (Table 1). Moreover, the addition of human IL-17A did not augment the production of NO in infected human MDM (Table 1). As human MDM did not produce NO in response to BCG infection, we decided to use RAW264.7 murine macrophages, which readily produce NO upon infection or stimulation,[15] as a model to study the effects of IL-17A on NO production in BCG-infected macrophages. We observed that IL-17A was able to synergistically enhance BCG-induced NO in a dose-dependent manner. The production of NO in macrophages was enhanced by 20%, 43% or 31% when pre-treated with 5 ng/ml, 25 ng/ml or 100 ng/ml of IL-17A, respectively. The IL-17A alone did not induce NO production in macrophages at all doses being tested (Fig. 1a). As IL-17A at 25 ng/ml had the greatest enhancing effect on BCG-induced NO production, we chose to use this concentration of IL-17A in all subsequent experiments. Next, we studied the kinetics of NO production and iNOS expression in BCG-infected macrophages. The macrophages were pre-treated with IL-17A for 24 hr, followed by BCG infection. The culture supernatants were collected at the indicated time-points for determination of NO production.

The resistive index (RI) on renal Doppler ultrasonography is a good indicator of renal vascular resistance as well as renal outcomes

in patients with chronic kidney disease (CKD). However, it is unclear whether the serum CysC level is associated with signs of vascular dysfunction, such as renal RI in CKD patients. Methods: We determined the levels of serum CysC in 83 CKD patients (median age: 57.0 years, male: 67.5%, diabetes: 9.6%) and investigated the relationship between the level of CysC and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse SB431542 molecular weight wave velocity (baPWV), a marker of arterial stiffness, and intima-media thickness (IMT), a marker of atherosclerosis. Results: The serum CysC level was significantly correlated with the renal RI (P < 0.0001)

and baPWV (P = 0.0001). The serum CysC level was a significant determinant of the renal RI (P = 0.0006), but not the baPWV or maximum IMT, in a multivariate regression analysis using a biomarker model. www.selleckchem.com/products/BKM-120.html The multivariate odds ratio of the serum CysC level for a renal RI of 0.70, a level that predicts worse renal outcomes, was significant (4.00, p = 0.0007); however, the odds ratios for the baPWV and maximum IMT were not significant. The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of CysC for predicting the RI 0.70 was 0.925 (P < 0.0001) (cutoff value: 2.04 mg/L). The serum CysC level was significantly correlated with the level of albuminuria and inversely correlated with the eGFR, as previously reported. Conclusion: The serum CysC level is independently associated with signs of vascular dysfunction, such as the renal

RI, in patients with CKD. The study VAV2 suggests that the serum CysC level serves as a novel and predictive marker of the renal RI in CKD patients. TAKAHASHI FUMIHIKO1,2, OKURA MINAKO1, WATANABE TOMONARI1, SASAGAWA YUTAKA1, HASEBE NAOYUKI2 1Rumoi City Hospital; 2Asahikawa Medical University Introduction: High salt intake is associated with hypertension and an increased risk of cardiovascular event. Restriction of salt intake is important lifestyle modification in Japan. Estimation of daily salt intake by spot urine method has been confirmed in some population studies, however the usefulness of this method in first-visit outpatients is unclear. Methods: Daily salt excretion was measured in 394 consecutive first-visit patients (58.4 ± 14.3 years old, female 54%) in cardiovascular outpatient clinic at Rumoi City Hospital. We excluded patients who had diabetes, advanced renal dysfunction, acute coronary syndrome and decompensated heart failure. We classified the patients into four groups according to the quartile of daily salt excretion (Q1: <8.2, Q2: 8.2–9.8, Q3: 9.8–11.7 and Q4: >11.7 g/day).

g. use of cytokines such as keratinocyte growth factor) or are associated with significant toxicity (e.g. androgen blockade).

One interesting new approach is the co-transplantation of pre-differentiated lymphoid progenitors together with uncommitted HSCs. Committed lymphoid progenitors Ceritinib are present in vivo only at extremely low frequencies, but can be induced experimentally in the presence of Notch-ligand expressing (e.g. Delta-like-1 or -4) stroma cells 2, 3. Several phenotypes of committed T/NK-lymphoid progenitors (CTLPs) have been described 4, 5, all of which are strongly biased toward T-cell and NK-cell lineage development and exhibit an enhanced thymus-seeding capacity. Two recent publications have reported a rapid intrathymic engraftment of human CD34+CD45RA+CD7+ lymphoid progenitors after intrahepatic transplantation in neonatal mice 6, BMS-777607 purchase 7. However, in these two models, no extrathymic

mature T cells could be detected, so it remained questionable whether a single intravenous injection of CTLPs can lead to peripheral T-cell engraftment. The aim of our study was to analyse the developmental potential of in vitro-generated CTLPs transplanted together with haploidentical, G-CSF-mobilised CD34+ peripheral blood (huCD34+) HSCs in a murine model of humanised chimeric haematopoiesis. Our results show that CTLPs further differentiate after co-transplantation with huCD34+ HSCs in vivo, but not in O-methylated flavonoid vitro, and create an early wave of peripheral T-cell re-constitution

at a time when progeny of huCD34+ HSCs is still at an early T-cell-progenitor stage. G-CSF-mobilised and purified huCD34+ HSCs were mainly lineageneg, CD34+38+, HLA-DR+CD117+, CD71+CD64− and CD45RA−CD7− (Fig. 1A and B). However, upon co-culture with OP9/N-DLL-1 stroma cells they rapidly acquired the described CD34+lineagenegCD45RAhighCD7+ phenotype (Fig. 1A, day 10) 4. Around 40% of cells acquired cytoCD3 and in part also CD5 by day 30 (Fig. 1C, upper plots); however, even after prolonged culture (until day 45 in two experiments), no expression of surCD3 (Fig. 1C, lower plots) or TCRαβ/γδ (data not shown) could be observed. About half of the CD7+ CTLPs expressed CD5 but only a minor fraction of these had already acquired CD1a (Supporting Information Figure 1A and B). As reported, CD4 increased after acquisition of CD5 or CD1a 6 but no CD4+CD8+ could be detected until the end of in vitro culture (Supporting Information Fig. 1B). To exclude that this maturation stop at the CD7+CD5+/−CD1a+/− level represents an intrinsic property of huCD34+ HSCs, we cultured CD34+-enriched cord blood progenitors (CB-CD34 HSCs) on OP9/N-DLL-1 stroma cells. Similar to their adult counterparts, CB-CD34 HSCs rapidly acquired the CD34+lineagenegCD45RAhighCD7+ phenotype but did not develop into mature CD3+ cells (Fig. 1B and C). Although two groups have reported the generation of mature single-positive T cells in OP9/DLL co-cultures 3, 8, others failed 7.

We previously showed that Treg cells play an important role in the protective response against T. gondii, since removal of Treg cells led to an increased mortality rate in the resistant BALB/c mouse strain 30. Moreover, treatment of T. gondii-infected susceptible C57BL/6J mice with

IL-2-anti-IL-2 complexes resulted in an increased Treg-cell frequency and survival, which correlated with reduced morbidity 31. Additionally, adoptive transfer of Treg cells has been reported to reduce the abortion rate in pregnant mice injected with excretory–secretory antigens from the XL765 mouse parasite 32. These studies demonstrate that Treg cells are important mediators of the immune response during T. gondii infection. The aim of this study was to determine whether Treg cells are involved in the immunosuppression observed during acute infection with T. gondii. ATM/ATR inhibitor We studied the suppression induced in C57BL/6J mice infected with the ME49 strain of T. gondii. We analysed the different cell subsets suppressed and characterized the Treg-cell population, including their suppressive capacity and expression of activation molecules. We evaluated the role of Treg cells in immunosuppression by selective elimination

of these cells using Foxp3EGFP mice and explored some possible mechanisms for Treg cell-induced suppression during T. gondii infection. In order to evaluate the suppression of different cell types during acute T. gondii infection, we analysed the mitogen-induced proliferation of splenocytes from C57BL/6J mice using CFSE. A representative FACS analysis (Fig. 1A) showed that proliferation of ungated splenocytes at 7 d

post infection (dpi) was slightly reduced when compared with cells from uninfected mice, but at 14 dpi the reduction was stronger. Cell proliferation, however, was completely restored at 21 dpi. The same proliferation pattern was observed in CD4+ T cells. The proliferation of CD8+ T cells at 7 dpi was comparable to that of Erythromycin cells from uninfected animals, but was dramatically reduced at 14 dpi, and was restored at 21 dpi, while LPS-induced B-cell proliferation was not affected. Accordingly, data from different experiments showed that the percentage of divided cells from the ungated population (Fig. 1B) is significantly reduced at 7 and 14 dpi. The percentage of CD4+ divided cells was halved at 7 and 14 dpi, while in the CD8+ subset it was only significantly reduced at 14 dpi. The percentage of CD19+ divided cells, however, increased approximately 30% and remained significantly higher during the period analysed. These data demonstrate that T. gondii-induced immunosuppression in Con A-stimulated splenocytes and in isolated CD4+ T cells observed by 3H-thymidine incorporation 15, 33 is also detected using CFSE dilution. Furthermore, we show that CD4+ and CD8+ T cells have different suppression patterns while CD19+ cells display an increased proliferation.

bilis (ATCC 51630). The authors showed that a rapid and persistent immunoglobulin G immune response to the organisms of the flora predated the development of colitis in infected mice and this was matched by a cytokine profile similar to

that seen in human IBD with elevated interferon γ (IFNγ), tumour necrosis factor α (TNFα), IL-6 and IL-12, but modest secretion of IL-10. The study suggested that perhaps the Helicobacter organisms are responsible for orchestrating an immune reaction, or loss of tolerance, to harmless members of the resident microbiota. A recent study by Matharu et al. (2009) has demonstrated the importance of a functioning Toll-like receptor 4 (TLR4) receptor in H. hepaticus-induced colitis. This study utilized MK-1775 mouse mice with TLR4-/-, IL-10-/- or both TLR4-/-and IL-10-/- and H. hepaticus (ATCC 51449). The dual-immunodeficient TLR4-/-× IL-10-/- mice demonstrated both an earlier onset and higher incidence of colitis than IL-10-/- mice. In addition, a dysregulated immune response

was seen after infection in the TLR4-/-× IL-10-/- mice with resultant IFN-γ/IL-17-secreting Foxp3+ Treg cell accumulation in the colonic lamina propria and a subsequent failure to control disease. This observation compliments the finding that genetic polymorphisms in MAST3, a TLR4 signal modulator confer an increased risk of human IBD (Labbéet al., 2008). Finally, Chow & Mazmanian (2010) have recently published a landmark paper examining the importance Saracatinib cost of the type VI secretion system (T6SS) to H. hepaticus (ATCC 51449) in terms of its activity being either symbiotic or pathogenic to the host organism. This study eloquently showed that wild-type T6SS organisms appear to promote an anti-inflammatory environment within intestinal epithelial cells (IECs) while mutant T6SS organisms show increased colonization of the murine intestine, increased intracellular colonization within IECs and, most importantly, a broad and apparently TH17-based host immune response to the presence of the organism. The study utilized various mouse models and a mouse IEC line. The importance of this study Liothyronine Sodium is that intraspecies

bacterial heterogeneity has been demonstrated to be as important as host heterogeneity in defining the ultimate host phenotype in an IBD model. The human story of Helicobacter infection with relation to IBD probably begins with the findings of Fennell et al. (1984) and Totten et al. (1985) from Seattle in the 1980s who isolated perhaps for the first, and only time since, novel Helicobacter organisms from colitic (and not simply diarrhoeal) humans. The humans in question were homosexual men with proctitis and the Helicobacter in question were isolated from rectal swabs, and classified at the time within the genus Campylobacter, labelled broadly as Campylobacter-like organisms (CLO). These CLO organisms were isolated from 33 of 201 (16.4%) symptomatic men and 14 of 155 (9.

Second, Singh and colleagues [10] demonstrated that a rise in ROIs and intracellular calcium are necessary

to amplify early BCR-induced phosphorylation signals. We have expanded upon their study and determined that both ER calcium release and CCE are redox regulated, suggesting that multiple calcium regulators are sensitive to oxidation and reduction and these changes control their function. Additionally, we have also identified reversible cysteine sulfenic acid formation as an oxidative modification this website necessary for both CCE and the signal transduction amplification loop following B-cell activation. Third, our CFSE experiment in the presence of dimedone clearly shows that reversible cysteine sulfenic acid formation is necessary for B-cell proliferation. This finding provides evidence that proteins necessary for B-cell proliferation transition through cysteine sulfenic acid

in order to exert their functions. Moreover, our data provides a mechanism by which antioxidant treatment decreases B-cell proliferation (Supporting Information Fig. 1S1) [26, 27]. Together, these observations provide Erlotinib in vitro a model in which ROIs positively regulate pathways in B-cell activation and proliferation through the reversible oxidation of cysteine residues in signaling proteins. This is a critical finding as it demonstrates that manipulation of ROIs and target pathways may improve B-cell responses

following vaccination or alternatively, dampen responses during autoimmunity. A previous study by Richards and Clark [9] demonstrated that BCR-induced ROI limits proliferation. However, we demonstrate that B-cell proliferation requires the production of ROIs for the reversible formation of cysteine sulfenic acid. How can the discrepancy between our studies be reconciled? There are many sources of ROIs including ER stress, mitochondrial electron transport chain (ETC), and NADPH oxidase enzyme enough complex (NOX) [28]. Using pharmacological inhibitors of ROI sources, Vené et al. [29] determined that the majority of ROIs is produced from complex I of the ETC and NOX following B-cell activation. The study by Richards and Clark [9] eliminates only one major ROI source, which functions to limit B-cell proliferation. Together, these studies suggest the source of ROIs could govern which proteins and pathways are targeted to either limit or promote B-cell responses. It is well documented that cysteine sulfenic acid formation in target proteins can either activate or inhibit protein function [13]. We clearly observe a global requirement for reversible cysteine sulfenic acid formation in B-cell proliferation; however, eliminating a particular ROI source could be driving an aberrant cysteine oxidation profile in target proteins, which could explain the altered B-cell proliferation kinetics.

The association of positive serological AMA in PBC patients with recurrent UTIs suggest a bacteria aetiology in PBC [7]. The hypothesis GSK126 that E. coli is a cause of PBC was first proposed in 1984, based on the higher prevalence of this bacterium in women in PBC when compared with age-matched women with other chronic liver diseases [13]. More recently, Varyani et al. reported that recurrent UTIs are present within 1 year prior to the diagnosis of in 29% of patients in PBC compared to 17% of non-PBC chronic liver disease controls [14]. This hypothesis is also supported by the

demonstration of T and B cell cross-reactivity between AMA epitopes and E. coli PDC-E2 sequences [24, 27, 41]. The induction of autoimmune

diseases is considered to Regorafenib manufacturer be the result of complex interactions between genetic traits and environmental factors, including microbial infections [42]. The microbial aetiology of PBC is poorly defined and the pathogenic mechanisms of biliary injury in PBC remain largely unknown. Clues indicating a microbial aetiological component to the pathogenesis of PBC were based largely on experimental evidence of B and T cell cross-reactivity between the major mitochondrial autoantigens and their mimicking microbial antigenic epitopes [27, 29, 43-50]. Additional support comes from epidemiological studies, case reports or molecular evidence of the presence of microbial or viral agents in the liver or bile specimens of patients with PBC [13, 29, 50-52]. Several hypothetical mechanisms, such as bystander activation of autoreactive cells, induction of proinflammatory cytokines by microbial antigens and molecular mimicry between the microorganism and the host have been proposed to explain how microbes initiate autoimmunity [9-12]. Among these hypotheses, the theory of molecular mimicry has been addressed rigorously Megestrol Acetate in PBC, which is based on the shared linear amino acid sequences or a conformational fit (for B cell cross-reactivity), or a motif (for T cell cross-reactivity) between a bacterial antigen and human ‘self’-antigen

[2, 28, 44, 53, 54]. An immune response directed against the mimicking microbial determinants may cross-react with the self-protein(s), and such autoreactivity may cause injury in targeted cells leading to cell destruction and, ultimately, autoimmune disease. In line with the theory of molecular mimicry, previously reported AMA cross-reactivity between the human PDC-E2 and its microbial counterparts in E. coli, N. aro and Lactobacillus delbrueckii suggested that PBC could be induced by exposure to these bacterial antigens [28, 42, 44, 55]. In addition, the identification of the 16S rRNA gene in livers from patients with PBC suggests that Propionibacterium acnes could be involved in granuloma formation in PBC [56].

trachomatis and C. suis. Immunoblot analysis, performed to elucidate the target of this neutralizing activity, showed a clear reactivity in human and pig sera against two proteins of 150 and 40 kDa MW, when tested either with C. trachomatis or with C. suis EBs. It is known that neutralizing species-specific or serovar-specific antibodies are produced in response to chlamydial infection in humans and in some animal species (Banks et al., 1970; Peterson et al., 1990; Girjes et

al., 1993; Donati et al., Kinase Inhibitor Library manufacturer 1996, 2006, 2009). The detection of these antibodies could be useful in the diagnosis of mixed infections or in the detection of immunogenic antigens as vaccine candidates. A previous study (Donati et al., 2009) reported a strong in vitro neutralizing activity to Chlamydia suis in 80% of Atezolizumab pig sera that, due to the presence of high microimmunofluorescence (MIF) titres, suggested C. suis infection. A close relationship

between C. suis and Chlamydia trachomatis has already been reported in relation to the ompA DNA sequence similarity (Kaltenboeck et al., 1997), together with morphology and other features, such as the production of glycogen in cell culture (Rogers et al., 1996) and the sensitivity to cathelicidins (Donati et al., 2007). In view of these features, in the present study, we evaluated the neutralizing activity against D–K C. trachomatis and C. suis purified elementary bodies (EBs) in sera collected from C. trachomatis-infected patients and C. suis-infected pigs. A total of 17 MIF chlamydia-positive selected sera were tested: 11 sera collected from C. suis-infected pigs showing C. suis neutralizing activity and six sera from patients infected with D, E, F, G, H and K C. trachomatis serovars, respectively. As a negative control, 10 human and 10 pig MIF chlamydia-negative sera were used. Before performing the neutralization assay, human and pig sera were diluted at a MIF titre of 128 to C. trachomatis and C.

suis, respectively, to obtain a uniform 3-mercaptopyruvate sulfurtransferase antibody concentration. Italian urogenital C. trachomatis isolates D–K (Donati et al., 2009), and the Italian C. suis isolate 7MS06 (Donati et al., 2007) were grown in LLC-MK2 cells and EBs were purified by sucrose density-gradient ultracentrifugation using the method of Fukushi & Hirai (1988). In addition, purified EBs of the reference strains Chlamydia muridarum Nigg, Chlamydophila pneumoniae IOL-207, Chlamydophila psittaci 6BC and the Italian Chlamydophila felis FEIS-M isolate were used to check the species-specificity of neutralizing antibodies in the human and pig sera. EB preparations were titrated to contain 4 × 105 inclusion-forming units (IFU) mL−1 and stored frozen in 0.25 M sucrose–10 mM potassium phosphate–5 mM glutamic acid, pH 7.4 (SPG), at −70 °C. As a source of complement, aliquots of fresh rabbit serum were stored at −70 °C and used in the neutralization assay at a 5% final concentration.

Apoptosis on the other hand may inactivate IL-33. It is likely that both inactivation and release of IL-33 take place linking between apoptosis and cell damage in many chronic inflammatory diseases in which Decitabine molecular weight IL-33 has been detected. The crucial role of IL-33 in asthma has been assumed due to several pieces of evidence. Administration of IL-33 results in lymphocyte-independent airway hyperreactivity, goblet

cell hyperplasia and eosinophilic and monocytic infiltration. Hypertrophy and enhanced mucous secretion in the bronchi and bronchioles occurs after repeated applications in mice 5. In addition, IL-13-dependent differentiation of alveolar macrophages towards alternatively activated macrophages with increased airway inflammation has been reported in a murine model 19. Furthermore,

CD34pos progenitor cells express the receptor for IL-33, ST2, and secrete large amounts of Th2-type cytokines and chemokines in the presence of IL-33. IL-13- and IL-5-expressing CD34pos cells have been found in the sputum of asthmatic individuals and were up-regulated upon allergen-challenge 12. Moreover, IL-33 contributes to the recruitment and activation of eosinophils to the same degree as IL-5. The in vivo relevance of IL-33 in human asthma is further supported by its higher expression in epithelial cells and smooth muscle cells in moderate to severe asthmatics, but not mild asthmatics. This has been confirmed 5-Fluoracil at the protein level in broncheoalveolar lavage fluid 20. Finally, a genome-wide association study has reported the association between single nucleotide polymorphisms in the IL-33 gene and in the ST2 gene and an increased risk to develop asthma 21. In conclusion, IL-33 is evolving as a candidate molecule that acts on DCs and bridges innate and adaptive immune responses in the lung. IL-33 thereby affects both the development of allergic sensitization and the aggravation of lung inflammation. The study by Besnard et al. 13 demonstrates this in an elegant way, defining DCs as effector cells in vivo and confirming ST2-specific Thiamet G DC activation. However, further work is required to fully delineate the role of IL-33 in allergic disease. Conflict of

interest: The authors declare no financial or commercial conflict of interest. See accompanying article: http://dx.doi.org/10.1002/eji.201041033 “
“In this study, we investigated the characteristics of the infection and subsequent immunity induced by Strongyloides venezuelensis in Lewis rats. Animals were infected with 4000 L3 of S. venezuelensis and number of eggs per gram of faeces indicated an acute phase around day 8 and a recovery phase around day 32 after infection. A strong Th2 polarization during recovery phase was ascertained by a significant increase in IgG1 and IgE compared with that in the acute period. A shift in the cytokine profile confirmed these findings. A predominant production of IFN-γ during the acute phase was followed by IL-10 production during recovery.