Despite the lack of longitudinal data, multiple cross-sectional studies show an inverse association between renal function and FGF-23. A few studies have examined the potential of FGF-23 as a prognostic marker of CKD progression. The Mild to Moderate Kidney Disease (MMKD) study examined a prospective cohort of 177 patients with mild to moderate, non-diabetic CKD for a

median of 53 months.39 FGF23 was inversely associated with baseline eGFR, and baseline FGF-23 levels were a predictor of progression of CKD when adjusted for phosphate and Selleck Paclitaxel PTH. The lack of longitudinal measurement of FGF-23 and the biomarkers of CKD-MBD, however, was a major limitation of this study. The significance of the extremely high FGF-23 levels in dialysis patients has also been examined. In 103 non-diabetic haemodialysis (HD) patients serum FGF-23 levels of 7500 ng/L predicted

the future development of refractory SHPT.54 This may be due to a relative PLX4032 mouse resistance of the hyperplastic glands to FGF-23. High circulating levels of biologically active FGF-23 led to speculation of a direct, non-Klotho mediated toxic effect on FGF-R; however, Klotho independent activation of the FGF-R has not been conclusively demonstrated.26 The effect of FGF-23 on the activity of extra-renal 1α-hydroxylase and local tissue calcitriol synthesis and levels remains unknown. Despite numerous studies showing the association between biochemical markers Rutecarpine of CKD-MBD and FGF-23, only a few pilot studies have explored the effect of available treatments of SHPT on FGF-23 levels. Secondary analysis of the ACHIEVE trial, comparing the effect on PTH suppression of the calcimimetic agent cinacalcet plus low-dose calcitriol analogues to calcitriol analogues alone, examined the effect on FGF-23 in 91 HD patients.61

The study reported a significant 9.7% decrease in FGF-23 levels in the cinacalcet group, with these changes significantly related to alterations in calcium and phosphate concentrations but not PTH. Effects on FGF-23 were also studied in 40 normo-phosphatemic patients with CKD stages 3–4 and elevated PTH, when comparing phosphate binder treatment with calcium acetate or sevelamer therapy over a 6 week period.62 FGF-23 levels decreased from 107 to 54 pg/mL in the sevelamer group (P < 0.05), with non-significant reduction in the calcium carbonate group, and a decrease in PTH was reported in both groups. Another prospective study of 46 HD patients assessed the effect of sevelamer and calcium carbonate compared with calcium carbonate alone,63 reporting that after four weeks of treatment phosphate and FGF-23 levels were significantly lower in the combination group.

The major characteristics of the study group are summarized in Table 1. Soluble and insoluble antigenic fractions of Leishmania were obtained as described in the study of Brito et al. (10). PBMC was obtained from 40 mL of heparinized blood according to the study of Reis et al. (5). PBMCs (4 × 106 per tube/mL) were incubated with soluble (SOL, BYL719 cell line 1·25 μg/mL) and insoluble (INS, 2·25 μg/mL) antigenic fractions of Leishmania (37°C/5% CO2) for 48 h. Negative control cultures (basal) consisted of patients’ cells in medium only, and positive

controls consisted of cells stimulated 4 h prior to the end of the incubation period with phytohemagglutinin (PHA, 10 μg/mL) or with ionomycin (IONO, 500 ng/mL) plus myristate acetate (PMA, 50 ng/mL). Brefeldin A (10 μg/mL) was added to all tubes 4 h prior to the end of the incubation period selleckchem (48 h). After the incubation, the cells were stained with antibodies anti-CD4 or anti-CD8 (labelled with FITC) (BD Biosciences, San Jose, CA, USA) and afterwards fixed with 1% paraformaldehyde. Then, they were permeabilized and incubated with cytokine-specific antibodies against IFN-γ, TNF-α, IL-10 (Miltenyi Biotec, Bergisch Gladbach,

Germany) and IL-4 (BD Biosciences) labelled with PE. Afterwards, they were resuspended with 1% paraformaldehyde and analysed (20 000 events/tube) through flow cytometry (FACSCalibur; BD Biosciences) using the software Cellquestpro™ (BD Biosciences) for acquisition and analysis of data. For intragroup

comparative analysis, the Wilcoxon test was used, and to detect differences between groups, the Mann–Whitney U-test was used. Buspirone HCl All the results were analysed considering the value of P < 0·05 statistically significant. In a phenotypic analysis of patients and controls responding T cells after a 48-h culture with the soluble and insoluble antigenic fractions of Leishmania and the mitogens PHA or PMA plus ionomycin, the amount of CD4+ and CD8+ T cells and the CD4/CD8 ratio were determined. The percentage of CD4+ T cells was higher and significantly different in cultures without or with different stimulus when compared to the values obtained by the control group. The percentage of CD8+ T cells was slightly superior in controls when compared to patients, although without statistical significance (data not shown). Under stimulation with the mitogens PHA or PMA plus ionomycin, CD4+ T cells had similar cytokine productions, and PMA plus ionomycin was found superior to be in the stimulation of CD8+ T cells to produce the cytokines TNF-α, IFN-γ and IL-4. Overall, CD4+ T cells were the main responsible factor for the production of inhibitory cytokines such as IL-10 and IL-4 and CD8+ T cells, especially under PMA plus ionomycin stimulation, and produced more Th1 cytokines such as TNF-α and IFN-γ (Figure 1a with significant results).

These findings suggest encouraging possibilities for targeting angiogenesis (for instance with anti-VEGF) PF-01367338 clinical trial as a therapeutic strategy in pilocytic astrocytoma. “
“Adult-onset GM2 gangliosidosis is very rare and only three autopsy cases have been reported up to now. We report herein an autopsy case of adult-onset GM2 gangliosidosis. The patient developed slowly progressive motor neuron disease-like symptoms after longstanding mood disorder and cognitive dysfunction. He developed

gait disturbance and weakness of lower limbs at age 52 years. Because of progressive muscle weakness and atrophy, he became bed-ridden at age 65. At age of 68, he died. His neurological findings presented slight cognitive disturbance, slight manic state, severe muscle weakness, atrophy of four limbs and no extrapyramidal signs and symptoms, and cerebellar ataxia. Neuropathologically, mild neuronal loss and abundant lipid deposits were noted in the neuronal KU-57788 cell line cytoplasm throughout the nervous system, including peripheral autonomic neurons. The most outstanding findings were marked neuronal loss and distended neurons in the anterior horn of the spinal cord, which supports

his clinical symptomatology of lower motor neuron disease in this case. The presence of lipofuscin, zebra bodies and membranous cytoplasmic bodies (MCB) and the increase of GM2 ganglioside

by biochemistry led to diagnosis of GM2 gangliosidosis. “
“S. Sharma, R. Bandopadhyay, T. Lashley, A. E. M. Renton, A. E. Kingsbury, R. Kumaran, C. Kallis, C. Vilariño-Güell, S. S. O’Sullivan, A. J. Lees, T. Revesz, second N. W. Wood and J. L. Holton (2011) Neuropathology and Applied Neurobiology37, 777–790 LRRK2 expression in idiopathic and G2019S positive Parkinson’s disease subjects: a morphological and quantitative study Aims: Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have been established as a common genetic cause of Parkinson’s disease (PD). The distribution of LRRK2 mRNA and protein in the human brain has previously been described, although it has not been reported in PD cases with the common LRRK2 G2019S mutation. Methods: To further elucidate the role of LRRK2 in PD, we determined the localization of LRRK2 mRNA and protein in post-mortem brain tissue from control, idiopathic PD (IPD) and G2019S positive PD cases. Results: Widespread neuronal expression of LRRK2 mRNA and protein was recorded and no difference was observed in the morphological localization of LRRK2 mRNA or protein between control, IPD and G2019S positive PD cases.

I.n. application of the nanogel-associated antigen was also efficacious, with the chitosan/alginate nanogels displaying the most noticeable effect in terms of reducing cerebral parasite load. Protection was mostly associated with a mixed Th1/Th2 response, but there was no clear indication that either a Th1- or Th2-biased response would

favour protection or reduced cerebral parasite load. Further studies are necessary to elucidate the potential mechanisms that lead to protection, particularly the role that the nanogels may be having on innate immune defence mechanisms. Overall, chitosan-based nanogels represent an innovative platform for both i.n. and i.p vaccination approaches to limit the disease caused by N. caninum infection. The authors wish to thank Joachim Müller for his invaluable help in statistical analysis and Norbert Müller for great support and helpful suggestions during the course of the project. J.P. Dubey (USDA, Beltsville, selleck screening library USA) is gratefully acknowledged for the kind gift of the N. caninum Nc-1 isolate. This work was made possible through the National Science Foundation (grant No. 31-127374). “
“Gamma interferon-inducible lysosomal thiol reductase (GILT) is an enzyme that catalyzes thiol bond reduction

and plays an important role in the early steps of antigen processing. The key factor involved in the regulation of GILT expression upon cell stimulation with interferon-γ (IFN-γ) is signal transducer and activator of transcription 1 (STAT1). In this click here study, we examined the role of STAT1 in regulating the constitutive expression of GILT. We showed that STAT1 interacts with the GILT promoter, even in the absence of IFN-γ, and that STAT1 represses GILT expression. These results reveal an atypical negative regulatory

role for STAT1 in the constitutive regulation of genes involved in antigen processing. Thiol reductases are enzymes that carry out the oxido-reduction of disulphide bonds in proteins.1 They are located in various cellular compartments such as the mitochondria,2 PRKACG endoplasmic reticulum3 and lysosomes.4–6 Gamma interferon-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase that reduces disulphide bonds under the low-pH conditions found within lysosomes. Through the reduction of thiol bonds of endocytosed proteins, GILT unfolds native protein antigens in preparation for subsequent processing by lysosomal proteases. The mature form of GILT is a 30 000 molecular weight (MW) enzyme, which has the conserved active-site motif (-CGAC-)1,3 typical of thiol reductases. However, it functions at an acidic pH of 4·5–5·5, and thus differs from other thiol reductases that function at neutral or alkaline pH.7 GILT is constitutively expressed in professional antigen-presenting cells (APCs),8 but also in T cells9 and fibroblasts.10 GILT is also secreted in tissue culture supernatants of GILT-expressing B-cell lines.11 GILT protein expression is moderately increased upon treatment with interferon-γ (IFN-γ).

The percentage of annexin A5 single-positive

cells (early apoptotic cells) was calculated within the viable population of cells. Enumeration of hypoploid cells was carried out as described previously [25, 26]. Briefly, cell pellets were resuspended and fixed with 70% ethanol for 2 h at −20°C. Subsequently, cells were centrifuged and resuspended in PI incubation buffer (45 mM Na2HPO4, 2·5 mM citric acid and 0·1% Triton X-100) for 20 min at 37°C. PI was added to a final concentration of 10 μg/ml. All cell preparations were examined with a FACSCanto II (BD Biosciences) using the diva software Histone Methyltransferase inhibitor (BD Biosciences) for analysis. Doublets were ‘gated-out’ by making use of a two-parameter measurement scheme in which a plot of

pulse peak height versus area (integral) PI signal allowed for identification and exclusion of doublets. The principles and components Protein Tyrosine Kinase inhibitor of RT–CES™ (ACEA Biosciences Inc., San Diego, CA, USA) technology have been described previously [27-29]. Briefly, the RT–CES system allows for non-invasive monitoring of target cells by using impedance sensor technology. Electrode impedance, which is displayed and recorded as cell index (CI) values, reflect the biological status of monitored cells, including the cell number, cell viability, morphology and adhesion quality. We monitored the effects of purified IgG from a subgroup of PAH (n = 16), SSc (n = 12) and SLE nephritis (n = 6) patients and healthy controls (n = 6) on HUVECs with the RT–CES™ system. We performed three experiments with the RT–CES™ system, each experiment with different HUVEC batches but with the same purified IgG from the above-mentioned subgroups. HUVECs were seeded at a density of 4500 cells per well on 96-well plates integrated with microelectrodes at the bottom of the wells (E-plates™; ACEA Biosciences Inc.). Briefly, cells were trypsinized, centrifuged and resuspended those in culture medium consisting of RPMI-1640 with Glutamax-1 (Gibco) supplemented with 10% iFCS (Integro BV) and counted. Background measurements were

taken after adding 50 μl of the culture medium to the wells of the E-Plate™. Cells were adjusted to the appropriate concentration, and 100 μl of the cell suspension was added to the E-plate™ wells. Thereafter, cell attachment, spreading and proliferation were monitored every 15 min using the RT–CES system. The cells were in the log growth phase after approximately 2–3 h after seeding, depending on the HUVEC batch used in the respective experiment. At this point, being similar within each HUVEC batch, the cells were treated with 160 μg/ml patient or control IgG in triplicate and monitored continuously for 48 h. HUVECs incubated in culture medium without iFCS (cell starvation) and HUVEC treated with 5 nmol/ml staurosporine in 10% iFCS served as internal positive controls for apoptosis. Data were analysed with spss statistical software version 15·0 for Windows.

29,30 Aluvihare et al.26 showed in elegant studies that murine Treg cells mediate maternal tolerance to the fetus, and their recruitment to the uterus was independent of the presence of conceptus but hormonally regulated. Furthermore, it was shown that adoptive transfer of CD4+ CD25+ Treg cells can rescue abortions in abortion-prone mice.31 While the murine studies have been concordant, human studies are limited for ethical reasons and show inconsistent results mainly regarding peripheral Treg cell changes during pregnancy. Such discrepancies might be explained by various reasons among which defining the Treg cell populations and methodological considerations like flow cytometric

gating and gestational time of sampling might play a role. Early studies24,25,27,32 reported increasing numbers of circulating Treg cells as pregnancy progresses, peaking at the second trimester and declining at the XL765 chemical structure end of pregnancy and postpartum while others could not confirm these changes. A recent comprehensive study33 showed, on the contrary, a decrease in the number of circulating Treg cells in the second term of normal pregnancy that was probably hormonally induced. Selleck GDC0068 Pathological conditions, such as recurrent abortions and infertility, have been connected to decreased numbers of circulating systemic Treg cells in the patients both during and after pregnancy.25,30 In most studies evaluating

Treg cells during human and murine pregnancy, the constitutive and high expression of CD25 was used as a

hallmark of the Treg cell subset.23,25,27 Few studies have addressed the importance of Foxp3 as a lineage marker of Treg cells L-NAME HCl during early human pregnancy.21,33 Furthermore, to our knowledge, reports on other Foxp3+ cell populations in paired decidual and peripheral blood samples are scarce or absent. In the current study, we aimed to characterize the phenotype, cytokine mRNA profile and distribution of decidual- and peripheral blood Treg cells in paired blood and decidual samples from healthy pregnant women with emphasis on the Foxp3 expression. Our investigation confirmed that in early normal pregnancy, CD4+ CD25++ Foxp3+ and CD4+ CD25+ Foxp3+ Treg cells are locally enriched in decidua. In contrast to previous studies, the numbers of these cells in peripheral blood of women in early pregnancy did not differ from those of non-pregnant controls. Moreover, we report for the first time that a population of the recently described ‘cryptic’ CD4+ CD25− Foxp3+ cells34 is indeed present and exclusively enriched in human normal early pregnancy decidua compared with peripheral blood. In total, 29 consecutive decidual samples of which 19 were paired with peripheral blood samples from early normal pregnancy and 15 peripheral blood control samples from healthy non-pregnant women were included in the study.

However, the authors caution that the applicability of these findings is reduced because the reporting of each outcome was limited to one or two trials in the meta-analysis.12 There is little evidence that calcium supplementation alone is effective in maintaining bone mineral density or reducing bone fracture risk. In a double-blind randomized controlled trial, Torres et al. studied the effects of daily low dose (1500 mg)

calcium supplementation in the first year post-transplant compared with a combination of this treatment with vitamin D supplementation (0.5 µg every other day) for the first 3 months post-transplant. They found that the combination treatment was more effective at preserving bone mineral density at the hip.16 A similar finding Forskolin order was reported by Uğur et al.17 who, in Buparlisib a randomized trial, compared four treatments: daily supplementation of 3 g calcium and 0.5 µg calcitriol; 3 g calcium carbonate with 0.5 µg calcitriol and nasal calcitonin; 3 g calcium alone; and no treatment. They showed that calcitriol with daily calcium supplementation abates the usual decrease in bone mineral density, however, they were unable to show a significant improvement in bone mineral density, possibly

due to small sample size and short duration of follow-up. There are no published studies examining the potential role of diet per se in preventing and treating bone disease in adult kidney transplant recipients. Meta-analysis of randomized controlled show that any intervention (bisphopshate, vitamin D sterol or calcitonin) for bone disease in kidney

transplant recipients reduces the risk of fracture in this population. These agents have also been shown to provide a statistically significant improvement in bone mineral density when given after transplantation, however, the clinical significance of this difference remains uncertain. There is little 5-FU chemical structure evidence that calcium supplementation alone is effective in maintaining bone mineral density or reducing bone fracture risk. Kidney Disease Outcomes Quality Initiative:18 No guideline on nutritional management including vitamin D or calcium. Recommendations regarding monitoring of serum calcium, phosphorus and intact parathyroid hormone. UK Renal Association: No recommendation. Canadian Society of Nephrology: No recommendation. European Best Practice Guidelines:19 Recommendations include: 0.25–0.5 µg/day calcitriol or 600 IU cholecalciferol; 1000 mg/day calcium (1500 mg post-menopause); treat persistent severe hypophosphatemia and hypomagnesaemia; cessation of smoking; and initiation of exercise. International Guidelines:20 Minimum calcium intake 1500 mg.

Thus, the role of γc signaling in T-lineage

cell development and differentiation needs further clarification. γc is a 64 kDa transmembrane protein that is the central signaling component for a series of cytokines, including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 [3]. In T cells, the major targets of γc signaling are primarily antiapoptotic molecules. In recent years, yet another role of γc as a prometabolic signal has Akt inhibitor gained much attention. As such, absent γc signaling was found to cause cellular atrophy with lower metabolic activities and reduced cell size [9, 12]. Mechanistically, γc signaling activated Akt and the mammalian target of rapamycin, resulting in glucose transporter-1 (Glut-1) upregulation and ribosomal S6 kinase activation to increase glucose consumption and anabolic processes, respectively [13-15].

Thus, the prosurvival function of γc is likely a combined effect of antiapoptotic and prometabolic activities. Hence, replacing γc’s survival function with molecules from the antiapoptotic arm of γc signaling alone is probably insufficient. In this regard, the serine/threonine kinase Pim1 provides an attractive solution to assess γc requirement in vivo, because buy Romidepsin Pim1 exerts both antiapoptotic and prometabolic activities. Pim1 is a proto-oncogene originally identified as a proviral insertion site of the Moloney Murine Leukemia Virus (MoMuLV). Overexpression of Pim1 conferred Protirelin growth factor independent cell survival and proliferation both in vitro and in vivo [16, 17]. Moreover, earlier studies with an Eμ enhancer driven transgenic Pim1 mouse demonstrated that the Pim1 transgene was expressed in all lymphoid lineage cells [18], and that it increased overall thymocyte numbers in cytokine signaling deficient mice [16, 17]. In agreement with such effects, Pim1 had been identified as an immediate downstream effector of γc cytokine signaling [19]. Specifically, Pim1 expression was induced upon γc cytokine signaling in T cells and prevented programmed cell death by inactivating the proapoptotic factors Bad and PTP-U2S

[20-22]. Additionally, Pim1 also upregulated metabolism by promoting glycolysis and activating the translational regulator, eukaryotic initiation factor 4E (eIF-4E) [23-25]. Thus, Pim1 is uniquely positioned downstream of γc to induce both antiapoptotic and prometabolic signals for T-cell survival. In this study, we introduced an Eμ enhancer driven transgenic Pim1 [18] into γc-deficient mice to restore both arms of γc prosurvival function. In such Pim1TgγcKO mice, we found that most T-lineage cells, including γδ T cells, NKT cells, FoxP3+ T regulatory (Treg) cells, and CD8αα intraepithelial lymphocytes (IELs) still failed to develop and survive. On the other hand, Pim1 greatly promoted αβ T-cell development in the thymus and improved peripheral αβ T-cell numbers.

Nevertheless, membrane CD127 expression by T cells is required for the Ab-mediated effects, so that the presence of a T-cell reservoir such as the

BM, in which recirculating memory CD8+ T cells downregulate CD127, might represent an obstacle to the effectiveness of the proposed therapy. This study helps to define the CD127 transcription upstream and downstream events in activated T cells, with implications for human therapies with IL-7, IL-15, and other T-cell-stimulating cytokines [[42]]. For example, in IL-7 clinical trials, reduced CD127 mRNA amount and lower membrane CD127 expression by T cells could underlie the T-cell proliferation decline that was observed after 1 week of continued administration of IL-7, despite high IL-7

level in blood [[2, 42]]. In these patients, the reduced CD127 expression by T cells was possibly due to a direct effect of IL-7, although other mechanisms cannot be excluded. Taken together, selleck screening library our findings show that CD127 membrane downmodulation by CD44high memory CD8+ T cells in the BM is driven by IL-15 and suggest that transcriptional and/or post-transcriptional mechanisms are involved. A better knowledge of CD127 modulation by activated T cells is relevant for human therapies acting on the IL-7/CD127 Selleck Ku 0059436 axis, such as novel treatments for cancer, HIV infection, GVHD, prevention of transplant rejection [[2, 40, 41]]. C57BL6/J (B6) mice were purchased from Harlan Nossan (Corezzana, Italy),

Acetophenone Charles River (Calco, Italy), or bred in the specific pathogen-free (SPF) mouse facility of S. Raffaele Biomedical Park Foundation, Castel Romano, Rome (SRBPF). IL-15 KO [[29]] and IL-15Rα KO mice [[26]] were bred at Research Center Borstel facility, Borstel. IL-7 KO mice [[43]] were a kind gift by D. Finke (University of Basel, Basel, Switzerland). CD127tg mice were kindly provided by I. Munitic and J. D. Ashwell (National Institutes of Health, Bethesda, MD, USA) [[30]]. From litter of CD127tg B1 line hemizygous mice, we selected mice with very high expression of membrane CD127 in peripheral blood T cells for further breeding; colony was maintained in the SRBPF SPF facility. In our experiments, we used female mice from 6 to 28 weeks of age, all on a B6 background. Mice were housed at the Department of Histology and Embryology facility, University of Rome “Sapienza”, according to the institutional guidelines (authorization no. 16/2008-B by Italian Minister of Health). Sentinel mice were screened as previously described [[10]]. Single cell suspensions were prepared from spleen, LNs (axillary and inguinal), and BM of individual mice. Cells were stained as previously described [[11]]. The following mAbs were used (all from Becton Dickinson Biosciences, San Jose, CA, USA) conjugated with fluorescein isothiocyanate (FITC), phycoerythrin (PE), phycoerythrin-Cy7 (PECy7), peridinin chlorophyll protein (PerCP)-Cy5.

Lien et al. recently showed that Irf5−/− mice were impaired in their generation

of antigen-specific IgG1 by T cell-dependent or T cell-independent immunogens. [[33]]. A similar analysis revealed contrasting data demonstrating increased antigen-specific IgG1 production from Irf5−/− LBH589 manufacturer mice [[24]]. To clarify the role of IRF5 in generating antigen-specific IgG1 and to determine whether the observed increase in IgG1 hypergammaglobulinemia in Irf5−/− mice (Fig. 2A) results in elevated IgG1 autoantibody production, we analyzed autoantibody isotypes in Irf5+/+ and Irf5−/− mice 6 months postpristane injection. As expected, IgG2a/c and IgG2b autoantibodies against dsDNA, RiboP0, U1A, U1B′/B were absent or significantly reduced in pristane-injected Irf5−/− mice (Supporting Information Fig. 1A and data not shown). Similarly, serum anti-RiboP0 and anti-U1A

IgG1 levels were significantly reduced in Irf5−/− mice, whereas anti-dsDNA IgG1 autoantibodies were similar between Irf5+/+ and Irf5−/− mice (Fig. 2B). Given INCB024360 that Irf5−/− mice have intact IgG1 class switching, the impaired production of certain IgG1 autoantibodies in this model of murine lupus supports the existence of a mechanism(s) other than class switching for the regulation of IgG1 autoantibodies by IRF5. Furthermore, the reduction in IgG1 anti-U1A, but not dsDNA, autoantibodies indicate that the TLR7-IRF5 axis is important for the development of pristane-induced autoantibodies and controls autoantibody

specificity. T helper (Th) 1 and 2 cells promote the production of IgG2a/c and IgG1, respectively; Th1-mediated autoimmune responses next generate the more pathogenic autoantibodies and are thus associated with the progression of murine lupus [[34]]. Imbalance of Th1 and Th2 cytokine homeostasis is a prominent feature of both experimental and human SLE [[35, 36]]. Given that IRF5 has been linked to proinflammatory cytokine expression [[17]], and several cytokines, such as IL-4, IL-5, IL-6, and IL-10, are known to promote antibody production [[37-41]], serum cytokine levels in PBS- and pristane-injected Irf5+/+ and Irf5−/− littermates were measured using the MILLIPLEX mouse kit (Millipore, Billerica, MA, USA). As early as 2 weeks postinjection, serum levels of the Th2 cytokine IL-10 were significantly elevated in Irf5−/− mice compared with those of Irf5+/+ mice (Fig. 3A); 6 months postinjection, only Th2 cytokines IL-4 and IL-5 were upregulated (Fig. 3B). There was no difference in serum levels of the Th1 cytokine IL-12p40 (Fig. 3C). As expected, serum levels of IL-6 were decreased in Irf5−/− mice, whereas TNF-α levels remained unchanged between wild-type and Irf5−/− mice (Fig. 3C). The increase in serum Th2 cytokines may contribute to disease protection in Irf5−/− mice since Th2 cells promote production of the least pathogenic IgG1 isotype [[34]] observed in Irf5−/− mice (Fig. 2A).