Thus, different cell populations coming from the draining area of peripheral LN were identified, and after antigen administration were analysed in more detail. Numerous studies focus on the presence of pLN for immune response induction. One study concerns the impact of the cervical LN (cLN) of rats in activation of the immune system after antigen was microinfused into the cerebrospinal

fluid [38]. It was shown that the cLN respond in an antibody producing manner for antigen which comes from the central nervous Tyrosine Kinase Inhibitor Library nmr system, and furthermore, after removing the LN, the antigen-specific antibody titre in the serum was perceptably reduced. It was concluded that the LN is important for the induction of a humoral immune response to central nervous system antigens

[38]. After recognizing the cLN as the brain-draining LN, Phillips et al. hypothesized that the LN play a role in multiple sclerosis (MS) as well as in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. MS is thought to be an organ-specific autoimmune disorder and/or a chronic inflammatory disease of the central nervous system [39] (for more detail see [40]). Genetic risk factors [human leucocyte antigen (HLA) haplotypes] and also environmental factors (Epstein–Barr virus, smoking and sunlight find more exposure) were identified in MS development [40]. Pathological demyelination of different brain areas (cerebrum, brain stem or spinal cord) with axonal destruction was found. So far, CD4+ T cells Methane monooxygenase and CD8+ T cells (adaptive immune system) have also been related to the disease, as well as natural killer (NK) cells, which belong to the innate immune system. All these cells were detected in higher numbers in the patients or specifically in the lesions [39,40]. Furthermore, anti-inflammatory therapies and immune modulation are beneficial to the disease process [39]. The deep and superficial cLN were removed, EAE was induced and a reduced enhancement of the disease was found. Different areas in the brain were analysed for EAE lesions and significant differences were found between LN-resected and LN-bearing rats [17]. It was concluded

that removing the LN leads to a break in the pathway of immune cells into the brain which reduces the lesions found normally in EAE. More than 10 years later this study was repeated and expanded by van Zwam et al., who were able to show variations at different stages of the disease (acute, chronic and chronic relapsing EAE) which seem to be cLN-dependent. Furthermore, they concluded that tolerance of antigen from the brain is not induced in the cLN [27]. Thus, they believe that the brain-draining LN could be a useful target for therapeutic strategies against MS. The effect of cLN dissection on immunoglobulin (Ig) production and S. pneumoniae colonization after nasal vaccination with pneumococcal polysaccharide was also analysed.

6C). Both tested cell lines AT9283 mw being transfected with the expression construct encoding c-Jun displayed a significantly more open chromatin configuration at the TNF TSS, as compared with cells transfected with control vector (Fig. 6D). The classical method to probe chromatin conformation—DNase I sensitivity assay [53, 54]—was previously

applied to the TNF/lymphotoxin (LT) genomic locus in different types of immune cells [14-17, 19-22, 24, 55]. DNase I hypersensitivity (DH) sites, the hallmarks of open chromatin, were found at the proximal TNF promoter and at TSS in primary and cultivated myeloid cells from mice, humans, and pigs [14-17, 19-22], and were confirmed by restriction enzyme accessibility assay in the mouse macrophage cell line J774 [18]. Results obtained with MNase this website digestion assay applied to human myeloid cell lines appeared controversial: closed chromatin configuration (putative nucleosomal positions) was identified either at the proximal

promoter [56] or at the proximal promoter and TSS of the TNF gene [57]. However, open conformation of TNF proximal promoter/TSS in mouse BMDM (GEO entry GSE26550 [58]) and human CD14+ monocytes (GEO sample GSM1008582) was confirmed by genome-wide DNase-seq analysis (Supporting Information Fig. 1). Open chromatin conformation at the TNF promoter in Jurkat T-cell line was detected only after stimulation or ectopic expression of viral proteins [15, 21, 55], and no studies were performed in primary

Org 27569 human T cells. The exact position of the DH site upstream of the TNF gene in primary mouse T cells was a matter of controversy. It was originally mapped to the middle of the intergenic region between TNF and LTα genes and designated “HSS-0.8” (hypersensitive site; “0.8 kb upstream of the first exon” [24]), but was recently remapped to the proximal part of TNF promoter [59]. This DH site appeared more prominent in cells polarized under Th1 conditions [24]. Analysis of recent DNase-seq data deposited to ENCODE [60] and GEO databases (GSE33802 [61]) confirmed the presence of DH site at the proximal TNF promoter with enhanced DNA accessibility at TNF TSS upon polarization of naive CD4+ T cells under Th1 conditions (Supporting Information Fig. 1A). DNase-seq analysis of the TNF/LT locus in human immune cells also revealed an open chromatin conformation at TNF promoter (Supporting Information Fig. 1B). In our study, we detected inducible chromatin remodeling at the TNF TSS of both mouse and human primary T cells by restriction enzyme accessibility assay (Fig. 1). We also confirmed the open status of TNF TSS in BMDM and detected inducible changes of chromatin conformation at TNF TSS in T cells by MNase digestion assay (Fig. 2).

While typical infant ERP studies create average waveforms for subjects with a minimum of 10 good trials, because the recruitment of full-term HII

infants with only mild-to-moderate HII injury was especially limited (as, for example, HII is much more common Selleckchem RG7204 in premature infants), we used more liberal exclusionary criteria at this stage in processing. Average waveforms were then visually examined by an experimenter with expertise in infant ERP who was blind to participant group, and infants were excluded if the averaged waveforms showed excess noise for at least one of the three conditions. The number of subjects lost at each phase of ERP processing is described in Table 4. Of subjects who wore the EEG net for at least 20 trials per condition, 57% of CON (16/28) and 75% of HII (6/8) were accepted into the final analysis. For the final sample, the mean number of accepted trials did not differ between CON (M = 37.13, SD = 6.93) and HII (M = 42.67,

SD = 11.62); t(20) = −1.39, p = .18, d = 0.67). Analyses focused on two regions: (1) frontocentral electrodes, which were grouped into left (19, 24, 29, 30), middle (5, 6, 12, 13, 112, VREF), and right (4, 105, 111, 124) regions of interest, and (2) temporal electrodes, which were grouped into left (34, 38, 44, 45, 46) and right (102, 108, 114, 116, 121; see Figure 2). Mean amplitude values for the Nc and PSW components were extracted for each individual participant for each stimulus condition at each of the scalp regions (averaging each amplitude value within the specified https://www.selleckchem.com/products/ABT-263.html time window). The time windows for the Nc and PSW were determined, using prior work on infant ERP waveforms as a guide (de Haan, Johnson, & Halit, 2003; Nelson & McCleery, 2008), by examining the grand mean average waveforms

for all CON and HII subjects, collapsed across condition, to narrow in on the time windows encompassing the components of interest in our group of infants (see also Figures 3 and 4). Nc mean amplitude was calculated to include the negative deflection occurring between 175 and 650 ms following stimulus onset, and the PSW mean amplitude was calculated to include the subsequent positive deflection Molecular motor occurring between 750 and 1,500 ms following stimulus onset. For the 18 CON and six HII that contributed sufficient data from the VPC familiarization phase and all three test delays, there was no difference in total looking during familiarization (CON: M = 15.8 sec, SD = 3.8 sec; HII: M = 16.8 sec, SD = 3.4 sec; t(22) = −0.55, p = .59, d = .28). A preliminary ANOVA including test version as the between-subjects factor revealed no main effects of this variable, and the present analysis therefore collapsed across this factor.

Although adhesion in itself may be independent of signaling, it was demonstrated that PECAM-1–PECAM-1 interactions increase expression of the integrin α6β1, which is involved in the migration process, on transmigrated neutrophils 25, and that PECAM-1 is essential for neutrophil chemotaxis 26. While the suppressive effect on migration exerted by PIR-B is in accordance with the anticipated function of an inhibitory receptor, the enhanced migration induced by

Ly49Q and PECAM-1 activation is perhaps unexpected. This raises selleck inhibitor the question whether these inhibitory receptors specifically enhance migration and suppress other effector functions. Indeed, PECAM-1 has opposing effects on inflammatory cytokine production and cell migration, illustrating that not all cellular functions are suppressed. Individuals carrying genetic mutations that lead to a disturbed inhibitory receptor function may be prone to develop excess leukocyte activation. Since some inhibitory receptors may be positively involved in cell migration, one could speculate that in individuals carrying mutations affecting such receptors, a reduced migratory capacity for cells with deficient

inhibitory Carfilzomib cost receptor signaling prevents tissue damage by infiltrated leukocytes. This perspective shows some similarity with the licensing theory in NK cells (which states that NK cells are “licensed” for functional competence by prior signaling through an inhibitory receptor 27) in which immune cells that have proper inhibitory

receptor function are licensed to migrate to the tissues. An ongoing immune response must be appropriately terminated to restore immune homeostasis. This process includes clearing of excess immune cells by apoptosis. Several inhibitory receptors may be involved in this process. CD33-related Siglec-8 and Siglec-9 are inhibitory receptors that have frequently Demeclocycline been associated with increased apoptosis in myeloid cells 28. In vitro, antibody-mediated cross-linking of Siglec-9 results in increased apoptosis in resting neutrophils 29 (Fig. 1). Moreover, inflammatory neutrophils obtained from patients with acute septic shock or rheumatoid arthritis demonstrated enhanced Siglec-9-mediated neutrophil death compared with healthy controls 29. The increased Siglec-9-mediated cell death could be reproduced by priming of neutrophils with pro-inflammatory cytokines, such as GM-CSF, IFN-α, or IFN-γ in vitro 29. This indicates that Siglec-9 may indeed have a role in regulating apoptosis of activated neutrophils to balance the immune response.

1% EDTA for 15 min with vigorous shaking at 37°C. (ii) Tissues were washed several times with 1× PBS, minced, and digested with Liberase (Roche) in RPMI for 30 min on an orbital shaker. (iii) Tissue was passed repeatedly through a 16 g 5-Fluoracil cell line syringe,

pelleted via centrifugation, resuspended in RPMI, and placed on 30–70% Percoll gradient. (iv) Cells were centrifuged at 2000 rpm for 30 min and mononuclear cells isolated from the interface. Cells were harvested, washed with 1× PBS, and subjected to FACS-staining protocols. FACS buffer (HBSS, 1% FBS, and 0.2% sodium azide) supplemented with anti-FcγRII/RIII mAb (2.4G2) and goat γ globulin (0.5 mg/mL) (Jackson Immunoresearch) was used to prevent nonspecific binding. In some experiments, the isolated mononuclear cells were incubated with a polyclonal PE-labeled mouse anti-human TGF-βRII or anti-mouse TGF-βRII (R&D systems), anti-CD11c (clone N418), anti-CD11b (clone M1/70), or anti-F4/80 (clone BM8) (eBioscience). Anti-mouse IL-33 (clone 396118) from R&D Systems

was used for intracellular staining following the addition of Golgi-stop (BD Pharmingen) for 2 h to inhibit protein transport. In some experiments, 7AAD was used to exclude dead cells from analyses. Acquisition was performed with a BD FACSCalibur and analysis was performed with Flojo 7.5.5 or Cellquest software. Colon PKA inhibitor tissue lysates were diluted in 1× PBS and subjected to the Proteome Profiler Array™ obtained from R&D Systems according to the manufacturer’s instructions. Ribonucleotide reductase Densitometric evaluation of blots was performed with a Bio-Rad Molecular Imager® Gel Doc™ system. ELISA was used to quantify murine IL-10, TGF-β,

and IL-33 (eBioscience). Statistical significance was assessed by either one-tailed Student’s t-test (two groups) or analysis of variance (ANOVA) for multiple groups with a post-hoc Tukey test to determine the significance performed using Prism Graph Pad™. The authors thank Amanda Roloson and Melissa Mingler for expert technical assistance and Marat Khodoun and Senad Divanovic for critical comments. Funding was provided by NIH grant R01GM083204 and the Department of Veterans Affairs. The British Heart Foundation supports D. R. G. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. “
“Specialized proresolving mediators are endogenous bioactive lipid molecules that play a fundamental role in the regulation of inflammation and its resolution. Lipoxins and other specialized proresolving mediators have been identified in important immunological tissues including bone marrow, spleen, and blood. Lipoxins regulate functions of the innate immune system including the promotion of monocyte recruitment and increase macrophage phagocytosis of apoptotic neutrophils.

Here, EC50 is the binding affinity in nM units and Th is the half-life in hours. In each of the five cross-validations, fourth-fifth of the data were used to train a given network, and one-fifth was used to determine when to stop the training in order to avoid overfitting. Upon training, each prediction method (affinity and stability) thus consisted of an ensemble of five networks. When using the networks to predict binding of a query peptide, the prediction score is calculated as a simple average over the five networks in the given

ensemble. The authors thank Sara Pedersen for excellent technical assistance and Kenneth C. Parker for reviewing this manuscript. This work was supported by NIH grant HHSN272200900045C. The authors declare no financial or commercial conflict of interest. “
“The 3′ regulatory region Selleck EGFR inhibitor (3′RR) located

Selumetinib research buy downstream of the IgH gene is the master element that controls class switch recombination and sustains high-level transcription at the plasma-cell stage. This latter role suggests that the 3′RR may be involved in oncogene deregulation during the frequent IgH translocation events associated with B-cell malignancies. A convincing demonstration of the essential contribution of 3′RR in lymphomagenesis has been provided by transgenic animal models. The mouse 3′RR shares a strong structural homology with the regulatory regions located downstream of each human Cα gene. Mouse models exploring the role of the 3′RR in B-cell physiology and in malignancies should provide useful indications about the pathophysiology of human cell lymphocyte proliferation. During precursor B-cell differentiation, genes encoding heavy (H) and light chains of an Ig molecule are somatically assembled from germline DNA. This process, named V(D)J recombination, occurs in the bone marrow prior to antigenic challenge. In germinal centers during the antigen-dependent stages, variable (V) regions become the target of somatic hypermutation (SHM) in activated B cells allowing the generation of high-affinity Ig. In mature B cells,

class switch recombination (CSR) deletes the constant (C) μ region and replaces it with a downstream CH gene. This enables B cells to express various Ig isotypes but still retain antigen specificity. Once activated, B cells differentiate Metalloexopeptidase into Ig-secreting plasma cells. During B-cell development all these events (V(D)J recombination, SHM, CSR, Ig synthesis) are coupled with transcriptional accessibility of the IgH loci. IgH transcription is controlled by the functional interactions of multiple promoters, enhancers and insulators spread among the 2.5 megabases of the locus. Among them, the upstream Eμ enhancer and the 3′ regulatory region (3′RR) stand out as major players. Chromosomal translocations linking oncogenes to these elements are often implicated as the cause of B-cell malignancies.

Based on the pharmacokinetics of 5 mg/kg described by Gervais et al.,[25] 250 μg of Pyl A was used for intrauterine injection. The CRTH2 antagonist GSKCRTH2X was obtained from Glaxo Smith Kline,

(London, UK) and 15dPGJ2 from Rucaparib cell line Cayman Chemicals (Ann Arbor, MI). Escherichia coli LPS serotype 0111:B4 (Sigma, St Louis, MO) was used in the murine model of inflammation-induced preterm labour. Human blood from non-pregnant women of childbearing age was collected in accordance with the South East London Ethics Committee approval Ref: 10/H0805/54, and in accordance with Imperial College NHS Healthcare Trust Research and Development department where recruitment took place. All blood was collected with written informed consent. Animal studies were performed under UK Home Office Licence 70/6906 and in accordance with the UK Animals (Scientific Procedures) Act of 1986, and the Imperial College Ethics Review Board. A protocol based on previous studies on CR3 (CD11b) expression was followed.[15] Four millilitres

of human blood was collected in sodium citrate vacutainers and the granulocyte fraction was isolated by incubating 1 : 1 blood : 4·5% Dextran (Fluka Analytical, Sigma, Gillingham, UK) in PBS for 45 min at 4°. The leucocyte fraction was centrifuged at 500 g for 10 min, and the pellet was resuspended in PBS containing CaCl2 (0·9 mm) and MgCl2 (0·5 mm) and counted. Cells were then pre-incubated at 37°, followed by treatment with Talazoparib molecular weight Etofibrate the CRTH2 agonists Pyl A or 15dPGJ2 for 15 min. The reaction was terminated by the addition of 1 ml ice-cold FACSFlow. In experiments with the CRTH2 antagonist, pre-incubation with GSKCRTH2X was performed for 10 min at 37°. The cells were then centrifuged at 400 g for 5 min at 4° and resuspended in PBS with 2% fetal calf serum for labelling with phycoerythrin-conjugated anti-CD11b and allophycocyanin-conjugated anti-CD49d for 10 min at 4° in the dark. The red cells were then lysed by

the addition of Optilyse-C for 10 min in the dark at room temperature. Cells were then washed and resuspended in PBS and 1% fetal bovine serum for analysis. Eosinophils were identified as CD49d positive and by high side and forward scatter. Flow cytometry settings were as follows: Forward scatter E0 Voltage, 1·00 Amp gain Lin, and Side scatter of 329 Voltage, 1·00 Amp gain Lin. CD1 outbred virgin female and stud male mice (Charles River, Margate, UK) were purchased at 6–8 weeks of age. All mice were housed in open cages at 21 ± 1°, on a 12 : 12 light : dark cycle regimen, with ad libitum access to standard chow and water. Timed mating was performed, with the presence of a copulatory plug being classed as E0 (day 0) of gestation. A mini-laparotomy was performed on embryonic day 16 (E16) of gestation correlating with human gestation of between 33 and 34 weeks.

In the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) report for 2007,8 4.0% of incident Australian patients have CAD, 19.0% have PVD and 13.0% have cerebrovascular disease. Similarly, the rates for incident dialysis patients from New Zealand are 13.0%, 25.0% and 15.0%, respectively. An analysis performed by Roberts

et al.9 using ANZDATA looked at adult incident dialysis patients between 1992 and 2002 and followed them to the end of 2003. During this time 18 113 patients were analysed. Patients with known CVD comprised 48.0% of the cohort and the remainder had no disease. In Australia, CVD was responsible for 51.0% of deaths. The age-specific cardiovascular mortality rate for patients without Selleck BYL719 CVD at baseline was 2.3 (1.9–2.8) per 100 person years in those aged 35–44 years, and increased to 11.9 (10.5–13.5) per 100 person years for patients aged 75–84 years (Fig. 1). Respectively, these

patients were 121 (98–149) and 5.7 (5.0–6.4) times more likely to die a cardiovascular death than people of similar age in the general population (Fig. 1). Similar findings were demonstrated in the New Zealand cohort. Few studies have assessed mortality rates or risk predictors selleck inhibitor in the period immediately after initiation of dialysis. These studies10–16 suggest an increased mortality rate in the first 90 days; however, it is not clear if this rise is limited to the first 90 days. All-cause and cause-specific mortality were examined in an incident United States cohort who began dialysis <30 days before enrolment into the Dialysis Outcomes and Practice Patterns Study (DOPPS) and had at least 1 day of follow-up (n = 4802).16 The risk of death was increased in the first 120 days compared with the period 121–365 days (27.5 vs 21.9 deaths per 100 person-years, P = 0.002). CAD was present in 51.8% of patients, cerebrovascular disease was present in 18.5% and other CVD was present in 29.1% of patients and CCF in

44.6%. Patients with CCF were at increased risk for mortality within 120 days of starting dialysis (adjusted HR 1.71 (1.35–2.17) P < 0.05) but not significantly different for other cardiovascular comorbid conditions. Similarly, in the 2007 USRDS report17 for incident 2004 patients, the overall mortality rate per 1000 patient years increased from 210.8 in month one to 307.8 in month three, ultimately falling to 246.1 in month Buspirone HCl 12. Overall, 1-year mortality rates were reported to be relatively stable since the 1990s. The USRDS data were recently used to analyse the outcomes of non-fatal myocardial infarction and cardiac death in incident dialysis patients from the years 1997–2001 (n = 214, 890).18 Multivariate analyses were performed employing Cox proportional hazards models using demographics, comorbidities, laboratory variables, body mass index, prior erythropoietin use and mode of dialysis. The relative risk of non-fatal myocardial infarction in patients with prior CAD compared with those without was 1.57 (95% CI: 1.5–1.

Analysis of the liver CD8+ T cells demonstrated that these cells segregate into at least two phenotypically distinct subsets of memory CD8+ T cells; the CD44hiCD45RBloCD62Llo effector memory set (TEM) and the CD44hiCD45RBhiCD62Llo/hi central memory set (TCM) (8). The CD8+

TEM cells are the major IFN-γ producers and their numbers decline with temporal loss of protection; the CD8+ TCM cells express increased level of IL-15R (CD122) (9) and require IL-15 for sustained homoeostatic proliferation (9,10). In addition, the CD8+ TCM cells play a role in the maintenance of protracted protection as the majority of IL-15 KO mice are protected upon a primary challenge but all lose protection upon re-challenge (U. Krzych, this website manuscript in preparation). Despite a decade-long effort to map T cell fine specificities of liver CD8+ TEM and PF-562271 TCM cells, we have only scant information regarding the potential pre-erythrocytic Plasmodia Ags that induce protective CD8+ T cells and the respective CD8+ and CD4+ T cell epitopes that complex with MHC class I and II to engage the TCR on protective T cells. One approach to examine the fine specificities of the CD8+ T cell subpopulations is to characterize and compare the TCR repertoire

in mice protected by immunization with Pbγ-spz (11–13). This approach would not only provide a much better understanding of the relationship between the liver-stage Ag-specific CD8+ TEM and TCM cells but might also suggest mechanisms by which plasmodial Ag are processed and presented to interact with TCR on effector T Atorvastatin cells. The TCR is expressed as a heterodimeric protein composed of α and β subunits. Somatic recombinations of diversity (D) and joining (J) regions in Vα, and variable (V), D and J regions in Vβ

result in the diversity of the TCR repertoire (14). A number of studies in mice (15–19) and humans (20–23) have demonstrated that preferential TCR Vβ are expressed during T cell responses to infectious agents that correlate with T cell function of a particular Ag specificity. These observations provided an impetus to ask whether T cells responding to a protozoan parasite like Plasmodium, which contains more than 5000 genes with approximately 2000 genes active during the liver-stage of development (24), would exhibit a narrow or a wide and fluctuating or a stable TCR repertoire during protective immunity. Surprisingly, the CD8+ T cell response to another protozoan parasite, Trypanosoma cruzi, with a genome encoding more than 12 000 genes, was found to be highly focused on epitopes encoded by members of the trans-sialidase family of genes (25). Moreover, responses to Toxoplasma gondii demonstrated that robust CD8+ T cell responses are directed to a single, dominant epitope (26).

At early time points, MSU-induced γH2AX levels in Nlrp3−/− and casp-1−/− DCs were comparable with those detected in WT DCs (Fig. 3A).

In contrast, 24 h MSU stimulation in the absence of NLRP3 or caspase-1 resulted in markedly decreased γH2AX levels. These data are consistent with the comet assay results underlining the likelihood of the NLRP3 inflammasome being involved in cellular responses to DNA damage. To confirm whether NLRP3 inflammasome activators directly induce DNA breaks, we used rotenone to provoke robust ROS production by mitochondria in order to activate NLRP3 learn more indirectly [10]. Similarly to MSU, rotenone treatment markedly induced γH2AX levels, which are reduced in both Nlrp3−/− and casp-1−/− DCs compared with WT (Fig. 3B). We also used camptothecin (campto), a topoisomerase I inhibitor, to promote DNA damage independently Cell Cycle inhibitor of ROS [11], and observed that the genotoxic effect induced by this drug was not lowered in either Nlrp3−/− or casp-1−/− DCs

(Fig. 3C). Finally, DNA damage induced by high-dose γ-radiation was also reduced in DCs lacking Nlrp3 and casp-1 after 24 h (Fig. 3D). Taken together, these results indicate that NLRP3 inflammasome may be involved in regulation of DDR. MSU, H2O2, rotenone, and γ-radiation all trigger the generation of ROS, which in turn react with DNA to cause base lesions. To clarify whether the DNA damage detected in DCs depended on ROS generation, we assessed ROS production following stimulation with MSU alone or in Immune system combination with LPS or H2O2 in DCs from WT and Nlrp3−/− mice. We did not observe any differences in the levels of MSU, LPS/MSU, or H2O2-induced ROS produced between WT and Nlrp3−/− DCs (Fig. 4A). However, after 8 h of MSU

exposure, ROS-mediated oxidative stress did induce upregulation of genes encoding the antioxidant proteins peroxiredoxin 1 and catalase more strongly in WT DCs than in Nlrp3−/− DCs (Fig. 4B). These data indicate that ROS generated by MSU treatment are equally abundant in WT and Nlrp3−/− DCs, but that they likely show a differential response in mediating redox and oxidative stress control. To test whether ROS did induce oxidative DNA damage following MSU stimulation, we assessed the formation of the DNA adduct 8-oxoguanine (8-oxoG), the major oxidation product and an important marker of free radical induced DNA lesions and oxidative stress [12]. We compared the proportion of 8-oxoG positive MSU-treated DCs prepared from WT and Nlrp3−/− mice. Following MSU treatment, the number of 8-oxoG positive nuclei was substantially increased in WT DCs compared with untreated controls (Fig. 4C and D). Importantly, the presence of 8-oxoG lesions was markedly lower in DCs deficient in Nlrp3, suggesting that the base excision repair system responsible for 8-oxoG repair in the DNA was more active in Nlrp3−/− cells than WT DCs.