In order to direct differentiation to kidney, we used human embryonic stem cells (hESCs) cultured in a fully chemically-defined monolayer culture. After 2–3 days of high BMP4 / low Activin A or high CHIR99021 alone, PPS was induced at over 90% efficiency. Ongoing culture without FGFs generated OSR1+ trunk mesoderm. However, the addition of FGF2 or FGF9 induced OSR1 together with the additional IM markers, PAX2 and LHX1,

by day 6 of differentiation. Timecourse RT-PCR from day 0 to day 18 showed that gene expression changed in a stepwise manner PPS to IM followed learn more by simultaneous induction of both kidney progenitor populations, the MM and ureteric epithelium (UE). By day 14 of differentiation, we observed synchronous induction of elongating epithelial PAX2+/GATA3+/ECAD+ UE together with a surrounding mesenchymal PAX2+/SIX2+/WT1+ MM. Within the dish, these populations formed a self-organising structure reminiscent of the embryonic kidney, including the formation of renal vesicles, the first phase of nephron formation. When these hESC-derived kidney progenitor cells were aggregated with cells from dissociated mouse embryonic

kidney cells and grown as an organoid ex vivo, hESC-derived components integrated into mouse-derived kidney structures, demonstrating the broad renal potential. When buy VX-809 aggregations were formed from hESC-derived cells only self-organizing events were observed, generating renal vesicles, proximal tubules and collecting ducts1. This differentiation was shown to be transferable to human induced pluripotent stem cell lines. The coordinated induction of cells from the various key cellular populations involved in kidney development demonstrates the requirement for interacting niches for the creation of complex morphogenetic structures. The capacity for such populations to undergo

self-organization in vitro bodes well for the future of tissue/organ bioengineering and the potential for pluripotent-stem-cell-based renal regeneration. 1. Takasato, Selleckchem AZD9291 M, Er, PX, Becroft, M, Vanslambrouck, JM, Stanley, EG, Elefanty, AG, Little, MH. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nature Cell Biology 16:118–126 (2014). LI PHILIP K.T. Honorary Professor of Medicine and Chief of Nephrology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong The discussion of evidence based treatment of IgA nephropathy (IgAN) is based on the work of Kidney Disease Improving Global Outcome (KDIGO) of which the author is on the board of Director and chairs the workgroup on the IgAN for the KDIGO Clinical Practice Guidelines for Glomerulonephritis.

Finally, FcR γ-chain-deficient mice are devoid of FcεRI and therefore any FcεRI-mediated effects of OVA-specific IgE during the sensitization or challenge phase, either due to mast-cell activation or altered DC function, is absent in these mice. Although the sensitization/challenge model that we used does not require B cells or antibodies, including

allergen-specific IgE, FcεRI, or mast cells 21, 22, it remains possible that in vivo FcεRI facilitated enhanced antigen-uptake or activation of pulmonary DC indirectly through mast-cell activation 23, 24. In contrast to previous studies 13, 14, 17 that employed BMDC and sensitization of FcγR-deficient mice, we aimed to specifically delineate the contribution click here of FcγR on lung DC during the challenge phase of the murine asthma model. We first confirmed the expression of FcγR expression on lung DC and compared their function to spleen-derived DC subpopulations, as the importance of considering the phenotypic, functional and anatomical differences of various DC subsets has been supported by several studies 25. Thus, our studies

focus on Ibrutinib chemical structure DC populations obtained from lymphoid organs in addition to pulmonary DC to study the function of FcγR. This revealed that lung DC and splenic CD8− DC gave rise to increased CD4+ T lymphocyte stimulation when DC acquired antigen as immune complexes via FcγRI, FcγRIII or FcγRIV. This effect was absent when CD8+ DC or FcR γ-chain deficient DC were used. These observations would be consistent with the view that contamination Idelalisib in vivo of OVA with endotoxins was not responsible for these alterations. Additional results support this interpretation. First, DC of TLR4-deficient mice led to increased T-cell proliferation after exposure to OVA-IC as compared to OVA alone. Second, serum of sensitized mice, which contained anti-OVA IgG, caused increased T-cell proliferation when given together with OVA to WT lung DC. This effect was antigen-specific, as serum of BSA-sensitized

mice did not cause this outcome, and FcγR-dependent, given that FcR γ-deficient DC did not result in increased T-cell proliferation. Several observations support the impact of FcγR on DC during the effector phase of pulmonary hypersensitivity. First, we adoptively transferred Th2-biased antigen-specific CD4+T lymphocytes 4 into antigen-naïve mice, thereby restricting the induction of pulmonary hypersensitivity mainly to the DC–T-cell interaction. Second, pulmonary exposure of mice to OVA-IC dramatically increased eosinophilia in the BALF and cellular infiltration in the lungs, an effect that was not observed in naive mice and thus not induced non-specifically. Third, the increased pulmonary immune reaction induced by OVA-IC was paralleled by a highly significant increase in proliferation of antigen-specific T cells, both in vitro as well as in vivo.

Recent data obtained with mice lacking the

transcription factor BATF3 (Table 1) indicate that this need not always be the case. Batf3-deficient mice, particularly on a 129/Sv genetic background, exhibit a selective block in the development of CD8α+ DCs and CD103+ CD11b− DCs [28, check details 29]. Notably, these mice display marked defects in the ability to mount cytotoxic T-cell responses to tumors and certain viruses, as well as in resisting parasites such as Toxoplasma gondii [28, 29]. Similarly, DT injection into Clec9a.DTR mice results in resistance to induction of cerebral malaria, probably because of a reduction in priming of Plasmodium-specific CD8+ T cells that induce pathology [29]. Finally, Langerin.DTR and DTA mice have revealed roles for LCs in immune responses and tolerance [14, 18]. Thus, the availability of mouse models for DC-subset depletion sheds light on the role of DC subtypes in immune regulation. CD11c.DTR and CD11c.DOG models are widely used to study the overall role

of DCs irrespective of subset. Importantly, both model systems display neutrophilia and monocytosis upon DT injection [18, 30]. This phenomenon had already been reported by Hochweller et  al. [9], but its functional implications have only recently begun to find more be appreciated. For example, a recent study by Tittel et  al. [30] observed increased bacterial clearance in DT-treated CD11c.DTR and CD11c.DOG mice as compared with noninjected controls in a bacterial pyelonephritis model. This unanticipated result was not Janus kinase (JAK) because the presence of DCs restrained bacterial elimination. Rather, it appears to be a by-product of the rapid influx of neutrophils into the kidney upon DT injection. Both CD11c.DTR and CD11c.DOG mice exhibit two waves of neutrophilia: An “early” wave that is manifest 24 h after DT injection and a “late” wave beginning at 72 h after DT injection. The

“early” neutrophilia is due to the release of neutrophils from the bone marrow in response to chemokines CXCL1 and CXCL2 [30]. In contrast, the “late” neutrophilia is a consequence of increased granulopoiesis, likely caused by increased levels of Flt3L (fms-related tyrosine kinase 3 ligand), similar to what has previously been observed in CD11c.DTA mice (Table 1), which constitutively lack DCs [31, 32]. A new CD11c-based DTR mouse model (CD11c.LuciDTR, Table 1) generated by Tittel et  al. [30] exhibits the ‘late’ but not the “”early”" neutrophilia upon DT treatment. Although the mechanism remains elusive, these data imply that the “”early”" neutrophilia does not result from a direct interplay between DC function and neutrophil recruitment, but, rather, relates to the actual mouse model used to deplete DCs.

Taken together, these results show that B. melitensis exopolysaccharide is a new mannose-rich polymeric structure. Besides exopolysaccharide, extracellular matrices often contain DNA, which may contribute to the structural integrity of biofilms (Whitchurch et al., 2002; Steinberger & Holden, 2005). To test whether Brucella’s clumps include DNA, culture samples were incubated in

the presence of DNAseI and the enzyme effect was observed under a microscope. Two hours after DNAseI incubation (Fig. 5b), clumps appeared to be digested by the nuclease while culture samples incubated with the enzyme buffer did not (Fig. 5a). This effect was increased after 24 h of incubation (Fig. 5c). Brucella melitensis wild-type strain or bearing a control vector (MG200 strain), used as negative aggregation controls, showed no effect of DNAseI treatment. These results Ulixertinib cell line demonstrate that DNA is a component of the

extracellular matrix of B. melitensis aggregates Sirolimus and contributes significantly to their structure. Because a recent study showed that OMVs are classical components of biofilm matrices (Schooling & Beveridge, 2006), we wondered whether our MG210 clumping strain could overproduce OMVs. We tested this hypothesis using transmission electron microscopy (TEM). We analyzed the abundance of OMVs’ structure in culture samples from MG210 and the wild-type strain collected in the stationary growth phase. Compared with the wild-type strain, we observed that the production of OMV-like structures was strongly increased in the clumping strain (Fig. 6a and b). Moreover, we took a set of minimum 20 TEM pictures for each strain on which we counted both the number of OMVs-like structures and the amount of bacteria to obtain quantitative data. Counting was performed in triplicate for each strain. As shown in Fig. 6c, we counted a mean of 73 OMVs per 100 bacteria in the

aggregative strain, but only four OMVs per 100 bacteria in the wild-type strain. These data indicate that OMVs could be a component of the matrix of the clumps formed by B. melitensis as described for other biofilm matrices. To confirm this hypothesis, we compared PRKACG the abundance of two major OMPs of the OMVs formed by Brucella (Omp25 and Omp31) (Gamazo & Moriyon, 1987; Boigegrain et al., 2004) in B. melitensis wild-type and MG210 strains by dot-blot analysis using specific MAbs (Cloeckaert et al., 1990). Omp16 (PAL lipoprotein) was used as an internal loading control. Dot blotting was carried out with B. melitensis culture supernatants (containing the OMVs fraction) (Fig. 7) from stationary-phase cultures. OD600 nm were used to normalize all samples. As shown in Fig. 7, the abundance of both tested OMPs of B. melitensis’ OMVs is strongly increased in MG210 supernatants compared with the control strain. Omp16 presented almost the same relative abundance in the two strains tested.

Although the mechanism of LAG-3 function remains unclear, a conserved KIEELE motif in the cytoplasmic domain of LAG-3 is essential 2. In contrast to CD4, LAG-3 is only expressed on the cell surface of activated T cells 1, 7–10. LAG-3 surface expression is further regulated by two metalloproteases, ADAM10 and ADAM17, which cleave surface LAG-3, a proportion of which is both constitutive and TCR-ligation induced 11. Importantly, prevention of LAG-3 cleavage blocks T-cell proliferation

and cytokine secretion 11 suggesting that LAG-3 surface expression is under tight regulatory control. This observation raised the question of whether other mechanisms are used to control the expression and distribution of LAG-3. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), which is another inhibitory molecule for T-cell activation, https://www.selleckchem.com/products/pci-32765.html is mainly stored in learn more intracellular compartments such as the trans-Golgi network, endosomes and lysosomes 12–17. Surface expression is tightly regulated by controlled internalization and trafficking to the plasma membrane. This raised the possibility that LAG-3 surface expression might also be regulated by modulating its intracellular storage and trafficking. In this study, we addressed the following questions.

First, what is the extent of intracellular storage and localization of LAG-3 versus its relative CD4? Second, what is the sub-cellular localization of LAG-3 and CD4 in activated T cells? Third, what is the fate of intracellular LAG-3? In order to determine cellular distribution of CD4 and

LAG-3, we performed intracellular staining for CD4 or LAG-3 using flow cytometry. Freshly isolated naïve CD4+ T cells do not express LAG-3 10; so naïve T cells were first stimulated with plate-bound anti-CD3 and anti-CD28 for 72 h and then treated with pronase to remove cell surface CD4 and LAG-3 from activated CD4+ T cells. Pronase treatment removed most of the surface CD4 and LAG-3 on activated T cells (Fig. 1A). While intracellular staining revealed that a relatively small amount (23%) of CD4 is present inside cells, in ifoxetine contrast a greater amount (49%) of LAG-3 appears to be retained intracellularly (Fig. 1A and B). One might speculate that the slightly lower LAG-3 surface expression compared with CD4 following T-cell activation and the increased percentage of intracellular LAG-3 versus CD4 is due to its continuous cleavage by the metalloproteases ADAM10 and ADAM17 that limits surface LAG-3 expression 11, 18. However, when T cells were treated with the metalloproteinase inhibitor TAPI (Calbiochem), cell surface LAG-3 expression was only slightly increased (data not shown). While prevention of LAG-3 cleavage by TAPI slightly changed the ratio of surface and intracellular LAG-3, the effect was small and not sufficient to account for the differences observed between LAG-3 and CD4. The extent of intracellular LAG-3 storage was also examined by Western blot analysis.

The cells were incubated for 96 h at 37°C in 5% CO2 and labelled with [3H]-thymidine (1·0 µCi/well) for the final 6 h of incubation. Cells were harvested LY2606368 mw onto glass wool fibre filters using an automated cell harvester and the [3H]-thymidine uptake was measured in a liquid scintillation counter. The counts are expressed as a stimulation index (SI), which was calculated by dividing the counts per minute (cpm) of stimulated cells by

the cpm of unstimulated cells. The phenotypic changes in the lymph node or spleen cells after TNF-α injection were assessed by staining the cells immediately after isolation with monoclonal antibodies (mAbs) against guinea pig major histocompatibility complex (MHC) class II, pan T (CT5), CD4 (CT7) and CD8- T cell (CT6) phenotypic markers (Serotec, Oxford, UK) using our previously published procedures [26,28]. For each mAb or control, 5–10 × 105 cells were incubated with mouse serum (Sigma) for 10 min to block FcR binding. This was followed by the addition of 50 µl of the appropriate antibodies followed by secondary staining with the fluorescein isothiocyanate (FITC)-conjugated AffiniPure goat anti-mouse immunoglobulin G (IgG) (H + L) (Jackson ImmunoResearch

Laboratories, Inc., West Grove, CA, USA). The proportions of positive cells were determined with a fluorescence activated cell sorter (FACS)Calibur flow cytometer and CellQuest software LBH589 concentration (Becton Dickinson Flavopiridol (Alvocidib) Immunocytometry Systems, San Jose, CA, USA). Spleen and lymph node cells were seeded into 24-well tissue culture plates (1 × 106 cells/well) and were stimulated with PPD (25 µg/ml) at 37°C in 5% CO2 for 24 h. Similarly, the peritoneal macrophages were cultured in the presence of PPD (25 µg/ml) or live M. tuberculosis[multiplicity of infection (MOI): 0·1] for 24 h. At the end of the incubation period, supernatants were removed and the cells were washed with phosphate-buffered saline (PBS), lysed with RLT buffer (Qiagen), and the lysates frozen at −80°C until RNA extraction. The total RNA from the spleen, lymph node and peritoneal macrophages

were isolated using the RNeasy kit (Qiagen, Valencia, CA, USA), as published earlier [29]. Taqman reverse transcription reagents (Applied Biosystems, Foster City, CA, USA) were used for reverse transcription and real-time RT–PCR was carried out using SYBR Green I double-stranded DNA binding dye (Applied Biosystems) and the ABI Prism 7700 sequence detector, as reported previously [26,29,30]. Real-time primers for guinea pig TNF-α, IFN-γ, IL-12p40, IL-10 and hypoxanthine–guanine phosphoribosyltransferase (HPRT) were designed using Primer Express software (Applied Biosystems), as reported previously [24,25,29]. Fold induction levels of mRNA were determined from the cycle threshold (Ct) levels normalized for HPRT expression and then to the Ct levels from unstimulated cells cultured for 24 h.

In a steady state, WASp exists in an autoinhibited form, and its activation is dependent on the activity of WIP (WASp interacting protein), Cdc42 (Cell division

control protein 42) and PIP2 (phosphatidylinositol biphosphate), upon which the C-terminus of WASp binds to and activates the Arp2/3 (actin-related proteins) complex [2]. The Arp2/3 complex stimulates actin polymerization by creating a new nucleation MK-1775 in vitro core, which is an initial step in the formation of actin filaments [3] and important for processes, such as cell motility, phagocytosis, and the formation of the immunological synapse (IS). As WASp is expressed in CD34+ stem cells and their progeny [4], patients with WAS display functional abnormalities in all hematopoietic stem cell-derived lineages, including neutrophils, monocytes, DCs, Langerhans cells, platelets, and lymphocytes. All lymphocytes, namely, B, T, as well as NK cells in patients with WAS exhibit Gemcitabine order anomalies in signaling as well as in the formation of the cytoskeleton [5, 6]. Regarding clinical symptoms, WAS is characterized by abnormal immune system functions, recurrent infections and inflammatory skin disorders such as eczema, and microthrombocytopenia. In

addition, WAS patients are at greater risk of developing autoimmune disorders. Similarly, Was−/− mice generated on 129, but not on C57BL/6, background have been reported to develop spontaneous colitis [7, 8]. Although the mechanisms of WAS-associated autoimmunity are not yet clarified, it has been proposed that this can be due to the bystander tissue damage during chronic inflammation or incomplete pathogen

clearance triggered DOK2 by the defective immune system, as well as due to loss of tolerance to self-antigens caused by defective localization and function of Was-deficient natural regulatory T cells [5]. Importantly, WAS patients also show a higher risk of developing hematopoietic malignancies already in childhood [9]. The higher incidence of tumors in WAS patients might depend on defective cancer immunosurveillance due to the WASp deficiency in the immune system; yet WASp mutations can also lead to cell genomic instability and tumorigenesis [10] so the situation is still unclear. This link between WAS and increased cancer incidence has been explored by Catucci et al. [11] in the present issue of the European Journal of Immunology. In order to test the hypothesis that Was deficiency affects tumor immunosurveillance in vivo, the authors crossed Was−/− mice to Cdkn2a−/− mice. The Cdkn2a (cyclin dependent kinase inhibitor 2A) gene codes for an important tumor suppressor [12] and Cdkn2a−/− mice are more prone to developing tumors [13]. Cdkn2a−/− Was−/− double knock-out (DKO) mice showed impaired survival, when compared to Cdkn2a−/− mice.

No transplantation-specific related interaction is documented, but in the context of impaired graft function, the use of sulphonylureas may be limited. In addition, the weight gain associated with these agents may exacerbate the weight gain often observed post-transplantation and worsen other metabolic risk profiles. Currently available thiazolidinediones, rosiglitazone and pioglitazone, Selleckchem AZD2281 are selective agonists of the peroxisomal proliferator-activated receptor gamma (PPAR-γ). They act as prandial glucose regulators and improve insulin sensitivity in adipose tissue, skeletal muscle and the

liver. They are efficacious and associated with a 0.5–1.4% reduction in HbA1c,3 although the long-term glycaemic durability may be superior with these agents.19 Pioglitazone has been shown to reduce the occurrence of some cardiovascular outcomes in patients with an eGFR less than 60 mL/min but at the risk of a greater decline in renal function.20 Rosiglitazone has been safely used post kidney transplantation and demonstrated good short-term efficacy,21 one of only two antiglycaemic medications with any evidence base post-transplantation (neither in the context of a randomized controlled trial). A previously released PPARγ agonist troglitazone was withdrawn because of several cases of fatal hepatotoxicity, but no similar problems have

been associated with either rosiglitazone or pioglitazone. Fluid retention (causing weight gain and reduced haematocrit), higher fracture rates

of distal extremities in women and some gastrointestinal Angiogenesis inhibitor side effects have all been observed with both agents. Caution is advised with PPARγ agonist use in patients with an eGFR less than 30 mL/min, although problems with fluid retention would be much more likely in the context of advancing chronic kidney disease. Of greatest concern, recent meta-analyses have shown that although pioglitazone is associated with a reduction in the incidence of death, myocardial infarct Cell press and stroke,22 similar analysis of rosiglitazone suggests an increased risk of myocardial infarcts and heart failure.23,24 This is despite both agents also showing mild benefits on other cardiovascular risk profiles such as hypertension and hypercholesterolemia. It should be highlighted that both rosiglitazone and pioglitazone are associated with fluid retention and congestive cardiac failure. Lago et al.25 demonstrated a class effect of thiazolidinediones on the occurrence of congestive cardiac failure, but not on cardiovascular death, in a meta-analysis of seven randomized, double-blind trials. Longer follow-up of such study patients is required to clarify the overall cardiovascular risk for patients on thiazolidinediones. The current advice regarding thiazolidinediones from regulatory authorities is specifically for rosiglitazone.

“
“Pathological heterogeneity of Aβ deposition in senile plaques (SP) and cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD) has been long noted. The aim of this study was to classify cases of AD according to their pattern of Aβ deposition, and to seek factors which might STI571 nmr predict, or predispose towards, this heterogeneity. The form, distribution

and severity of Aβ deposition (as SP and/or CAA) was assessed semiquantitatively in immunostained sections of frontal, temporal and occipital cortex from 134 pathologically confirmed cases of AD. Four patterns of Aβ deposition were defined. Type 1 describes cases predominantly with SP, with or without CAA within leptomeningeal vessels alone. Type 2 describes cases where, along with many SP, CAA is present in both leptomeningeal and deeper penetrating arteries. Type 3 describes cases where capillary CAA is RG7204 supplier present along with SP and arterial CAA. Type 4 describes a

predominantly vascular phenotype, where Aβ deposition is much more prevalent in and around blood vessels, than as SP. As would be anticipated from the group definitions, there were significant differences in the distribution and degree of CAA across the phenotype groups, although Aβ deposition as SP did not vary. There were no significant differences between phenotype groups with regard to age of onset, age at death, disease duration and brain weight, or disease presentation. Women were over-represented in the type 1 phenotype and men in type 2. Genetically, type 3 (capillary subtype) cases were strongly associated with possession of the APOE ε4 allele. This study offers an alternative method of pathologically classifying cases of AD. Further studies may derive additional genetic, environmental

or clinical factors which associate with, or may be responsible for, these varying pathological presentations of AD. Classically, Alzheimer’s disease (AD) can be defined as a progressive neurodegenerative disorder Ribociclib in vitro which presents as a disturbance of memory and cognition and is characterized histopathologically by the presence of numerous senile plaques (SP) and neurofibrillary tangles (NFT) within neocortical and certain subcortical regions, accompanied in most cases by a deposition of amyloid β protein (Aβ) in the walls of leptomeningeal and intracortical (parenchymal) arteries, arterioles, capillaries and veins, and known as cerebral amyloid angiopathy (CAA). The same Aβ protein deposited in blood vessel walls is also present in the brain parenchyma within the SP, although this is mostly composed of the longer peptide, Aβx-42, whereas CAA Aβ protein is mostly composed of the shorter peptide, Aβx-40 [1]. Nonetheless, the origins of CAA are still poorly understood. Various mechanisms have been proposed, which include a derivation from blood and or cerebrospinal fluid [2], local production by smooth muscle cells and/or pericytes [3] or through secretion from neurones and perivascular drainage [4].

68 Furthermore, the DTH response was diminished upon depletion of either CD4+ cells or either one of the human Th17-inducing cytokines, Fludarabine cost TGF-β or IL-1β68 suggesting that Th17-mediated responses alone are capable of mediating the DTH-like glomerular effects seen in patients with crescentic GN. Experimental autoimmune anti-GBM studies have demonstrated that mice deficient in IFN-γ were not protected from disease but developed more severe signs of clinical disease.69 More recently, we have shown that when compared with wild-type mice (IL-12 and IL-23 intact), IL-12p40- (IL-12 and

IL-23 deficient) and IL-23p19-deficient (IL-12 intact, IL-23 deficient) mice were protected from the induction of experimental autoimmune anti-GBM but IL-12p35-deficient (IL-12 deficient, IL-23 intact) mice were not.70 In this model, autoimmunity was induced in mice by repeated immunization with mouse alpha 3 chain Type IV collagen non-collagenous domain (α3(IV)NC1), which is the known target autoantigen in human autoimmune anti-GBM GN disease and Goodpasture’s disease.71 Autoreactivity to α3(IV)NC1 and

consequent renal injury was significantly reduced in the absence of IL-23.70 These observations suggest that IL-23 and hence the Th17 cell subset are necessary for the induction of autoimmune renal disease, which is consistent with other observations in autoimmune inflammatory selleck products models of multiple sclerosis11 and rheumatoid arthritis5 that have proven the IL-23-driven Th17 cell subset essential in autoimmune pathogenesis. Experimental models of planted foreign antigen crescentic GN (historically

known as ‘anti-GBM GN’, but without any autommunity) have also been used to study the role of Th17 cells in GN. In a study where, sheep antimouse GBM antibodies are used to induce GN, it has been shown that IL-17A- and IL-23p19-deficient mice are protected from glomerular injury.72 IL-17A upregulated the expression of pro-inflammatory chemokines: Sodium butyrate CCL2, CCL3 and CCL20 in mouse mesangial cells in vitro.72 It has also been shown, in separate experiments using this model, that Th17 cells use the chemokine receptor CCR6 (which binds to CCL20) to migrate into the kidney.73 There is growing evidence for the participation of IL-17A in systemic lupus erythematosus (SLE). IL-17A levels are elevated in the sera of patients with lupus74 and IL-17 positive CD4+ cells are present in SLE patients.75 IL-17A plasma levels correlated with activity (Systemic Lupus Erythematosus Disease Activity Index, (SLEDAI)), and ex vivo induction of IL-17A by IL-23 costimulated leukocytes from patients with lupus nephritis was significantly higher compared with healthy controls.75 Furthermore, IL-23 is upregulated in the plasma and peripheral blood mononuclear cell (PBMC) mRNA of SLE patients.75,76 Isolated PBMC from patients with lupus nephritis were shown to produce higher levels of IL-6 and anti-ds-DNA antibody than controls.