e. a specific quantitative phenotype. The mice are click here usually backcrossed a large number of generations onto a specific strain (usually C57Bl/6) and, as controls, the WT of the same strain is most often used. These types of experiments are, however, subject

to many pitfalls and there are no clear standard rules regarding how to perform and report them. As a result, incorrect conclusions may be drawn, which delays the discovery of the true effects. These problems have, over the years, been debated mainly based on examples where the targeted genes are located within loci that have been positioned in the genome by genetic mapping experiments, but the effect is subsequently found to be mediated by a gene(s) other than the one originally suspected in the locus (see 1–5). Mapping of genes controlling disease or immunological traits allows the identification of the chromosomal region containing the genetic polymorphism AZD3965 supplier of importance and subsequently, after great effort, the exact positioning

of the affected gene(s) can also be determined. This has revealed a very complex pattern of numerous polymorphisms that are spread over the genome of commonly used inbred strains. Isolation of such loci, i.e. introducing the loci to a new genetic background, may produce both stronger and different effects of the gene as has been shown using congenic strains containing defined chromosomal regions of a different origin. It has, for example, been reported that crosses of 129 and C57Bl/6 (B6) strains results in mice that spontaneously display a lupus type of systemic autoimmunity 3. Mapping the 129×B6 crosses showed that the autoimmune response is controlled by numerous loci. Thus, in mice NADPH-cytochrome-c2 reductase with a targeted gene within a linked 129 fragment backcrossed onto B6 there is a considerable risk that the targeted gene is influenced

by the surrounding 129 genes when autoimmunity is analysed. In fact, the authors demonstrate that a 129-derived congenic fragment of chromosome 1 containing both apcs and FcR genes has effects on lupus autoimmunity by itself, questioning the data using mice with knockout genes in the same 129-derived region 3. In another example, it could be shown that an unknown polymorphic gene, rather than the targeted interferon receptor deficiency, explained diabetes resistance 5. A similar explanation was provided for the effects of osteopontin knockout on autoimmune disease, which are found to vary depending on the number of backcrosses 4. The precise identification of mutations may change our understanding of the role of the gene, as previously determined by targeted deletions, as is the case with the contrasting effects of Ncf1 on autoimmune diseases 6–8. To have a conclusive experiment that analyzes gene modifications, it is necessary that only the gene in question is compared.

Millipore HA cellulose ester (MAHAS4510) was used for IgA ELISpot

assays and Immobilon P (MAIPS4510) membrane-bottom plates were used for IFN-γ ELISpot assays. For IgA ELISpots, the antigens used were recombinant nucleoprotein, recombinant listeriolysin, and sonicated WT listerial antigen. Antibodies in cultured lymphocyte supernatants were also harvested for soluble vaccine-specific immunoglobulins by ELISA, as previously described (25), an assay also known as the ALS assay (30). For IFN-γ ELISpots, control wells included phytohemagglutinin (PHA) and “CEF”, a commercially available standard peptide pool including 32 CMV, EBV and influenza virus peptides, 8–12 BGB324 supplier amino acids in length (AnaSpec, San Jose, CA, USA). Test peptides included the same three influenza peptide pools and the listeriolysin O (LLO) (25) peptide pool described above. The complex whole listerial antigen was also used in IFN-γ ELISpot studies. Spots were counted by an automated reader (Immunospot; CTL, Shaker

Heights, OH, USA). Low level spot counts in unstimulated medium-only control wells were subtracted from the test wells. The IFN-γ ELISpot results are presented as mean values of duplicate wells per condition as spot-forming Trichostatin A cells (SFC)/106 PBMC. A positive response for an individual was defined as more than two-fold greater than baseline results for that antigen and over 100 SFC/106 PBMC (31, 32). Because IFN-γ responses did not appear related to the oral dose given, results were also analyzed as a whole by organism given, comparing pre-immune with peak values. Serum samples were studied by ELISA to quantify IgG and IgA directed against sonicated listerial antigens, recombinant his-tagged listeriolysin and Influenza A nucleoprotein over time. Antigens were suspended in PBS and used to coat Nunc-Immuno Maxisorp 96-well plates (Nalge Nunc International, Roskilde, Denmark). Assays were performed as described (9) and read on a Vmax kinetic microplate reader (Molecular Devices, Sunnyvale, CA, USA).

Endpoint dilutions are reported as the highest dilution at which a serum sample was ≥0.14 OD units at 405 nm, an arbitrarily chosen cutoff value. Four-fold or greater increases in endpoint titer were considered a positive result. The differences in geometric means between groups were compared statistically with the Mann–Whitney PLEKHB2 test. Both vaccine strains were demonstrated by sequencing to contain the expected deletions and heterologous fusion antigen. The introduction of the attenuating mutations ΔactA/plcB and ΔactA/inlB did not significantly alter growth kinetics in TSB broth as measured by optical density, nor did the incorporation of the “empty” integration vector, pPL2. Introduction of the foreign antigen fusion cassette did moderately alter growth kinetics; both the rate of growth and the final density of growth were slightly depressed (OD600nm∼1.5 to 2.0 vs. ∼2.3 to 2.7).

We also now formally demonstrate activation of the inflammasome by Borrelia. When spleen cells of mice lacking IL-1β were stimulated with Borrelia, IL-17 production was significantly diminished, which also raises the hypothesis that the IL-1β is also involved in induction

of Th17 cells by Borrelia spp. IL-17 Palbociclib mw is associated with more severe disease progression in several autoimmune disorders, such as rheumatoid arthritis (RA) or multiple sclerosis 41. In patients diagnosed with RA, elevated levels of IL-17 were found in synovial fluid 42, 43. Since several clinical symptoms between RA and Lyme arthritis are similar, it has been proposed that IL-17 might be involved in the development of Lyme arthritis 10. In line with this hypothesis, it has been demonstrated that blockade of endogenous U0126 cell line IL-17 in IFN-γ-deficient mice results in complete protection against development of arthritis after infection by Borrelia 44. These data

indicate that controlling the IL-17 response by IFN-γ plays an important role in chronic Lyme disease. IL-33 is a member of the IL-1 family and is mainly involved in induction of T-helper 2-like cytokines, such as IL-4 and IL-5 23. Although it was shown that IL-33 is cleaved by caspase-1, the activity of the mature protein has never been assessed. IL-33 can be secreted from cells after caspase-1 stimulation 45, very recent data suggest that IL-33 activity is independent of caspase-1 46, 47. More recently, it was shown that IL-33 can be functionally active and binds to its receptor ST2 without being cleaved by caspase-1, and that this cytokine is more related to IL-1α than to IL-1β or IL-18 48. It was also described that IL-33/ST2 binding results in the regulation of mainly Th2 responses, which is in line with our results. IL-33 seems not to be involved in either IL-17 or IFN-γ production by Borrelia spp. 23. In this study, we also demonstrate that IL-33 does not play a role in the regulation of pro-inflammatory

cytokines such as IL-1β and IL-6 induced after Borrelia exposure. This study demonstrates modulation of IFN-γ/IL-17 responses by Borrelia spp. through mafosfamide inflammasome and caspase-1 activity. These findings are the first to demonstrate the existence of a counter-regulatory mechanism of Th1 versus Th17 cytokines during stimulation with Borrelia spp.. As shown in this study, IL-18 is crucial for the Borrelia-induced IFN-γ production, and IFN-γ has been suggested to be essential for induction of Th1 cells. Th1 cells drive cell-mediated immune responses and support the fight against invading pathogens. Induction of Th1 cells after recognition of Borrelia might be very important in the early immune response against spirochetes.

Accordingly, we found that R299W mutant was not impaired in any functional assay. On the contrary, its activity was slightly enhanced compared with WT FI on endothelial cells. The residue Asp501 is buried in the SP domain and is located next to the catalytic triad residues His362, Asp411 and Ser507 at the bottom of the S1 specificity pocket (Fig. 8). FI preferentially buy GDC-0449 cleaves peptide bonds after Arg or Lys residues, which insert into the S1 pocket and make a salt-bridge with Asp501. The change to Asn would impair this interaction and thus the function of the protein, but structure and stability should

be unaffected. This is observed experimentally both in the fluid phase and on cell surfaces. aHUS is a disease that during the last years has been associated with impaired regulation of the alternative pathway of complement. In more than 50% of aHUS patients one or several genetic abnormalities have been identified in complement inhibitors. FH is the inhibitor that has been most extensively studied and most of the aHUS-associated mutations reside in the C-terminal part of the protein, which is responsible for binding to cell surfaces 35. www.selleckchem.com/products/azd2014.html In these patients

either the FH concentrations are reduced or are normal but protein function is impaired, resulting in less efficient regulation of the alternative pathway. The mutations identified in C317 and FB16 are “gain-of-function” mutations since they make the C3 convertase more stable, resulting in the cleavage of more C3 molecules to C3a and C3b, in turn leading to the formation of more MAC and finally more cell lysis. The patients with MCP mutations usually Sclareol show a decreased expression of MCP but in some cases the protein is expressed normally but it shows impaired function 11. In this study,

the expression, secretion and function of FI mutations was examined. The nonsense mutations with pre-mature stop codons had impaired expression and secretion, whereas the missense mutations resulted in impaired expression and secretion or decreased function in solution or/and on cell surfaces. Since aHUS patients mainly show impaired regulation of the alternative pathway on the endothelial cells in the glomerulus, it is important to analyze the function of the FI mutants on the surface and not only in solution. Two mutants (P32A and A222G) had normal (A222G) or slightly reduced (P32A) activity in solution, reduced activity on the cell surface when FH was used as cofactor, but normal activity when membrane-bound MCP served as cofactor, as shown using two different methods. The D501N mutation nearly abolished activity of the proteins regardless of the cofactor used and form of C3b (in solution or deposited on a surface). Some mutations differed in effect depending on the cofactor used, for example H165R worked more efficient in the presence of C4BP and FH while it was not affected in the presence of CR1 and MCP.

The DiabCare Indonesia 2008, this was a non-interventional, cross-sectional study. It was recruited 1785 patients from secondary and tertiary medical centers across Indonesia that it was eligible for analysis. The mean age of the patients was 58.9 ± 9.6 years. The mean duration of diabetes was 8.5 ± 7.0 years. Majority (97.5%) of the patients had type 2 diabetes. 67.9% had poor control of diabetes (A1c:8.1 ± 2.0%).

47.2% had PD98059 FPG>130 mg/dL (161.6 ± 14.6 mg/dL). Dyslipidemia was reported in 60% (834/1390) and 74% (617/834) of those received lipid lowering treatment. Neuropathy was most common complication (63.5%); other complications were: Diabetic retinopathy 42%, nephropathy 7.3%, severe late complications 16.9%, macrovascular complications 16%, microvascular complications 27.6%. About 81.3% of patients were on OADs (± insulin), 37.7% were on insulin (±OADs). Majority used biguanides followed by sulfonylureas. Majority of the WHO-5 well being index responses fell in positive territory (Pradana et al, 2010). The DiabCare Malaysia 2008, analysis from 1549

patients showed deteriorating glycemic control with mean HbA1c of 8.66 +/- 2.09% with only 22% of the patients achieving ADA target of <7%. 80.3% of patients were hypertensive and 75% were on anti-hypertensive medication. 46% of patients had LDL levels > 2.6 mmol/L; 19.8% had triglycerides > 2.2 mmol/L; Compound Library 27.4% had HDL < 1 mmol/L despite 85% of the patients being on lipid lowering agents. Microvascular, macrovascular and severe late complications were reported in 75%, 28.9% and 25.4% patients respectively. The rates of diabetic complications were cataract 27.2%, microalbuminuria 7%, neuropathy symptoms 45.9%, leg amputation 3.8% and history of angina pectoris was 18.4%. Quality of life evaluation showed that about one third of patients have poor quality of life (Mafauzy et al, 2012). The DiabCare Philippines, a total of 770 diabetics were recruited from general hospitals, diabetes clinics and referral clinics, Adenosine triphosphate out of which 724 were type 2 diabetic patients. Results: The mean HbA1c was 8.03 ± 1.96 % and only 15.0% of the patients achieved ADA target of <7%.

2.5% of patients had LDL levels >2.6 mmol/L; 14.3% had triglycerides >2.2 mmol/L; 19.2% had HDL < 1 mmol/L and 53.9% of the patients were on lipid lowering agents. 68.4% patients were hypertensive and 64.4% were receiving anti-hypertensive medication. Microvascular, macrovascular and severe late complications were reported in 68.1%, 14.8% and 9.4% patients respectively. The rates of diabetic complications were cataract 32.7%, neuropathy symptoms 45.2%, microalbuminuria 15.8%, history of angina pectoris 10.7% and cerebral stroke 4.7% (Jimeno et al, 2012). The DiabCare Bangladesh 2008, results from 1860 diabetics showed deteriorating glycaemic control with mean HbA1c of 8.6±2.0% with only 23.1% of the patients achieving American Diabetes Association (ADA) target of <7%. 896 (47.0%) patients were hypertensive and 850 (94.

25 Renal hL-FABP binds to lipid peroxidation BGB324 nmr products generated by oxidative stress, and redistributes them into the tubular lumen, thereby preventing tubulointerstitial damage. Cisplatin is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas and some carcinomas. However, acute kidney injury is a serious side effect of cisplatin, thus, strategies to reduce acute kidney injury is important for continuation of cisplatin as a cancer treatment modality. This model is used to evaluate the pathophysiology of AKI after platinum-based chemotherapy. Intraperitoneal

injection of cisplatin in mice induces acute tubular necrosis and apoptosis, which are similar to the phenotypes observed in human cisplatin induced nephropathy. In the proximal tubules of this model, it was reported that metabolism of intracellular FFA was suppressed and nonesterified fatty acid and triglycerides accumulated

in kidney tissue. When the metabolism of FFA is activated by activation of the peroxisome proliferator-activated receptor (PPAR), the degree of cisplatin induced nephropathy is attenuated, therefore, increased intracellular FFA is considered to be closely associated with the generation and progression of nephropathy. Since there is a PPAR response element (PPRE) in the promoter region of hL-FABP, the presence of PPAR ligand, which activates PPAR, upregulates the expression of hL-FABP as well.30 In the cisplatin-induced nephropathy model, gene and protein expressions PLX3397 of hL-FABP are upregulated and urinary excretion of hL-FABP is also increased.26,27 Although the degree of tubulointerstitial

damage in the Tg mice is similar to those in the WT mice, accumulation of FFA in the kidney of Tg Pyruvate dehydrogenase mice is significantly inhibited and acute kidney injury in the Tg mice is significantly reduced by administration of PPAR ligand, which further upregulates the expression of renal hL-FABP. Further, urinary hL-FABP levels are decreased in the Tg mice administered both cisplatin and PPAR as compared to the Tg mice with cisplatin administration alone. From these results, it is concluded that more upregulation of renal hL-FABP by PPAR activation is protective of acute kidney injury in this model. Adenine is one of the two purine bases used in the formation of DNA and RNA. Adenine injected into the body is oxidized to 2,8-dihydroxyadenine (DHA) by xanthine dehydrogenase (XDH). Since DHA has low solubility in body fluid, injection of a large amount of adenine causes DHA to be filtered through the glomeruli and to accumulate in the tubular lumen, thereby leading to tubulointerstitial inflammation and subsequent tubulointerstitial fibrosis. XDH inhibitors, such as allopurinol, inhibit the production of DHA derived from adenine and attenuate adenine-induced nephropathy.

In humans, chronic exposure to asbestos is a key risk factor for development Proteasome inhibition of mesothelioma, suggesting that inflammasome-mediated inflammation might underlie the pathogenesis of this tumour. The link between

inflammation and cancer has prompted the evaluation of anti-inflammatory agents in tumour therapy 33. In myeloma, a plasma cell neoplasia localised to the bone marrow, there is a evidence that myeloma-derived IL-1β induces IL-6 production by bone marrow stromal cells, and this acts as a growth factor for proliferation of the myeloma cells. Blocking IL-1β with anakinra diminishes IL-6 production and, in a clinical trial, this treatment significantly reduced disease progression 36. Myeloma is often treated with thalidomide, and this agent has recently been shown to inhibit caspase-1 activity (and IL-1β secretion) in keratinocytes 37. This suggests that thalidomide, might act in myeloma via caspase-1 inhibition and the breaking of the IL-1β-IL-6 loop, targeted by Lust et al. 36. Furthermore, these studies suggest that targeting the action of IL-1β (e.g. by using anakinra or longer acting IL-1β inhibitors) might be a useful

alternative to thalidomide therapy. The link between inflammation and cancer should not always be viewed as detrimental, as there is a likely selleck inhibitor balance between inflammation that triggers productive anti-tumour immune responses and inflammation that promotes tumour progression

33. This has been demonstrated most strikingly by Ghiringhelli et al. 38. Extracellular ATP activates the inflammasome via purinergic receptors 26; ATP derived from dying tumour cells stimulates dendritic cell production of IL-1β, via the NLRP3 inflammasome, and IL-1β is required for optimal IFN-γ production by CD8 T cells and tumour elimination in vivo38. Although the study was performed using animal models, the authors also demonstrated that breast cancer patients harbouring a P2X7 receptor variant, with reduced affinity for ATP, were more likely to develop metastases. These results suggest that this pathway of ATP activation of the NLRP3 inflammasome, via purinergic receptors, is likely to emerge as a major player in the regulation of anti-tumour immunity. IL-1β is important in mediating chemically induced liver damage and Astemizole progression from an acute injury to liver fibrosis. This was demonstrated in IL-1R-deficient mice, which, following thioacetamide treatment, were partially protected against liver damage and had reduced fibrogenesis 39. The synthesis of IL-1β typically depends on the activation of two danger sensing pathways; the TLR pathway to stimulate production of IL-1 propeptide, and the NLRP3 inflammasome complex to process propeptide into a mature cytokine. The role of the NLRP3 inflammasome in this process, and in the context of the liver disease, was studied by two groups. Watanabe et al.

To lyse contaminating erythrocytes, 1 mL of 0.83% NH4Cl:Tris aminomethane 20.59 g/L, 9:1 (pH 7.2) was mixed with the precipitate and centrifuged at 1500 rpm for 5 mins at 4°C. Finally, the pelleted cells were resuspended in RPMI 1640 medium

with 10% heat inactivated FBS (Biowest, Nuaile, France). Viable cell numbers were counted with a hemocytometer by the trypan blue dye exclusion technique. Splenocytes were seeded in 12-well plates at a concentration of 2 × 107 cells/mL and restimulated with 0.5 mg/mL OVA. The plates were incubated at 37°C in a humidified 5% CO2 environment. The culture supernatants were collected after 24 and 72 hrs for measurement Lapatinib cell line of cytokines. The concentrations of cytokines in the supernatants were assessed by sandwich ELISA according to the manufacturer’s instructions (Duosets; R & D Systems, Minneapolis, MN, USA) and calculated by interpolation of cytokine standard curves. Student’s t-test was used for statistical analysis of the cytokine profiles. selleck compound IL-10, IL-13 and TNF-α were detected in the culture supernatants collected after 24 hrs, whereas IFN-γ and IL-4 were detected in those collected after 72 hrs. As shown in Figure 6, as evidenced by cytokine concentrations in the supernatants of the splenocytes,

there were no significant differences in IL-4, IL-10 or IL-13 production in OVA with pyriproxyfen-immunized mice compared to controls at Weeks 3 or 8. However, mice immunized with OVA with pyriproxyfen showed significantly greater concentrations of TNF-α on both Weeks 3 and 8 (907.9 ± 57.9 and 363.0 ± 72.8 pg/mL, respectively) than did controls (479.6 ± 59.7 and 149.1 ± 34.7 pg/mL; P = 0.04 and P = 0.03, respectively). In addition, as shown in Figure 6, the concentration of TNF-α on Week 3 was significantly higher than that on Week 8 (P = 0.02). The concentrations of IFN-γ were significantly higher at both time points (370.6 ± 45.34 and 273.0 ± 66.2 pg/mL, Urease respectively) compared to controls (83.5 ± 29.2 and 68.9 ± 32.9 pg/mL; P = 0.001 and P = 0.01, respectively). In alum containing OVA

immunized mice, the concentrations of IL-4 were significantly higher than those of controls (290.9 ± 22.1 vs. 113.3 ± 5.6 pg/mL; P = 0.001) on Week 8 only. The concentrations of IL-10 were significantly higher (700.2 ± 85.0 and 555.1 ± 32.1 pg/mL, respectively) than those of the controls at both time points (395.1 ± 92.8 and 420.9 ± 20.9 pg/mL, P = 0.04 and P = 0.01, respectively). However, there were no significant differences in production of IL-13 in OVA between alum-immunized mice and controls on Weeks 3 or 8. In the present study, particularly high IgG2a titers and upregulation of TNF-α and IFN-γ were observed in mice immunized with pyriproxyfen along with OVA, but not in those immunized with OVA in alum (Figs. 5 and 6).

A significant increase of newly produced proliferating CD34+ eosinophil-lineage-committed cells in vivo after allergen exposure (compared with the saline-exposed animals) was identified. It is noteworthy that almost all lung cells that stained positively for CCR3 check details also co-expressed MBP, which further argues for the eosinophil-lineage commitment of these CD34+ CCR3+ cells. In addition, we cultured CD34+ lung cells to assess their capacity to form CFUs in vitro after incubation with rmIL-5 alone, rmEotaxin-2 alone, or with the combination of rmIL-5 and rmEotaxin-2. Surprisingly, a significant increase in CFUs

compared with control was found in all three groups, arguing that eotaxin-2 itself can function as an eosinophilopoietic factor in the lung, expanding the previous findings that lung progenitors

can produce IL-5-dependent CFUs in vitro.9,24 Studies in humans have suggested a role of eotaxin-1 in the differentiation of CD34+ cells towards eosinophils because cord-blood-derived CD34+ cells cultured in the presence of eotaxin-1 differentiate into eosinophils.21 Furthermore, we have previously shown that CD34+ cells release markedly more IL-5 compared with the CD34− eosinophils, suggesting that the airway CD34+ cells may play an autocrine role in their final maturation to eosinophils.9 In contrast, we were unable to detect any colony formation of buy I-BET-762 BM CD34+ cells that were incubated with eotaxin-2 alone, suggesting that this chemokine only has haematopoietic function outside the BM. Taken together, these findings suggest that allergen-induced haematopoietic events do occur in the lung during allergen exposure, and that eotaxin-2 has haematopoietic effects alone or together unless with IL-5, primarily within the airways, whereas IL-5 has haematopoietic effects in the BM as well as in the lung. CD34+ progenitors

that co-express IL-5Rα are considered to be the earliest eosinophil-lineage-committed progenitor cell.4 CD34+ IL-5Rα+ cell numbers are increased in the mucosa of patients with atopic asthma compared with controls and CD34+ IL-5Rα+ as well as CD34+ CCR3+ cells have been shown to increase in BM, circulation and induced sputum in patients with allergic asthma compared with controls.4,12–14,36,37 The present study show that CD34+ CD45+ IL-5Rα+ eosinophil progenitors are increased in the airways after allergen exposure, confirming previous published data in mice and humans.4,22,36,37 However, we also demonstrate a significant increase in the proliferating IL-5Rα+ cells in vivo in the lung after allergen challenge. It is important to note that most of the IL-5Rα+ cells in the airways of allergen-exposed mice also co-expressed CCR3, which implies that these receptors may have complementary functions in the lung CD34+ cells.

However, among RD15 ORFs, only RD1504 (Mce3A)

induced a strong Th1 bias in healthy subjects and a weak Th1 bias in TB patients, whereas other ORFs of RD15 induced only moderate to weak Th1 biases or a Th0 type response in both TB patients and healthy subjects. These results further suggest that RD1504 (Mce3A) may have potential as a vaccine against GSK-3 inhibitor TB. This work was supported by the Kuwait Foundation for the Advancement of Sciences (KFAS) grant no. 2002-1302-04. The supply of buffy coat samples from healthy subjects through the Central Blood Bank, Kuwait, is gratefully acknowledged. “
“Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, China MicroRNA-155 (miR155) is required for antibody production after vaccination with attenuated Salmonella. miR155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin (Ig)G1 antibodies. In this study, we observed up-regulation of miR155 in the

peripheral blood AZD8055 datasheet mononuclear cells (PBMCs) of patients with myasthenia gravis (MG), and miR155 was also up-regulated in torpedo acetylcholine receptor (T-AChR)-stimulated B cells. We used an inhibitor of miR155 conjugated to anti-CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG (EAMG) mice. Our results demonstrated that silencing of miR155 by its inhibitor impaired the B cell-activating factor (BAFF)-R-related signalling pathway and reduced the translocation of nuclear factor (NF)-κB into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens Cytidine deaminase of EAMG mice. Our study suggests that miR155 may be a promising target for the clinical therapy of MG. “
“The purine nucleoside adenosine is an important anti-inflammatory molecule, inhibiting a variety of immune cells by adenosine receptor-mediated mechanisms. Invariant

NKT (iNKT) cells recognize glycolipids presented on CD1d molecules and produce vigorous amounts of cytokines upon activation, hence regulating immune reactions. The mechanisms polarizing their cytokine pattern are elusive. Previous studies demonstrated that adenosine can suppress IFN-γ production by iNKT cells. We describe the expression of all four known adenosine receptors A1R, A2aR, A2bR and A3R on mouse iNKT cells. We show that IL-4 production in primary mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade with an inverse relation to IL-4. These data are supported by A2aR-deficient mice, which exhibit largely decreased levels of IL-4, IL-10 and TGF-β concomitantly with an increase of IFN-γ upon α-galactosylceramide administration in vivo.