Ten thousand iNKT cells were collected in RLT buffer with 1% of β-mercaptoethanol. mRNA was isolated using RNeasy Mini Kit (Qiagen) and reverse transcripted with Superscript III (Invitrogen). Quantitative-PCR was realized with SYBR Green (Roche) and analyzed with LightCycler 480 (Roche). Pancreatic islet cells were prepared as previously described 53. Pancreata were perfused with a solution containing collagenase P (Roche), dissected free from surrounding tissues and digested at 37°C for 10 min. Islets were then purified Selumetinib order on a Ficoll gradient and disrupted by adding cell dissociation buffer (GIBCO) for 10 min at 37°C. iNKT cells from spleen and mesenteric LNs of CD45.1+/+ CD90.1+/+

Vα14 Cα−/− NOD mice were enriched by negative selection and then sorted as CD4− or CD4+ CD1d-αGalCer tetramer+ cells. Sorted cell purity was >96%. CD62L+ BDC2.5 T cells were isolated from CD45.2+/+

CD90.1+/+ BDC2.5 Cα−/− NOD mice. Splenocytes were enriched in T cells by negative selection and CD62L+ cells were positively selected using biotinylated anti-CD62L mAb and Streptavidin microbeads (Miltenyi Biotec). CD62L+ BDC2.5 T-cell purity was >92%. Similar procedures were used for the reconstitution with NK1.1− or NK1.1+ CD4− iNKT cells. Donor cells were obtained from NK1.1 Vα14 Cα−/− NOD mice. At selleck 2 wks of age, CD45.1+/+ CD90.1+/+ Cα−/− NOD mice were reconstituted i.v with 1.5×106 CD4− or CD4+ iNKT cells from CD45.1+/+ CD90.2+/+ Vα14 Cα−/− mice. Mice were injected i.p with PK136 mAb (50 μg/mouse of on days 15, 17, 26 and with 100 μg/mouse on day 32). At 6 wks of age, recipient mice were injected i.v with 104 naïve CD62L+ BDC2.5 T cells from CD45.2+/+ CD90.1+/+ BDC2.5 Cα−/− mice. Diabetes analysis was also performed in mice reconstituted with NK1.1− or NK1.1+ CD4− iNKT cells. In some experiments mice were injected i.p with 200 μg of blocking anti-mouse IL-17 Ab (CA028_00511) or isotype control (101.4) on days 0, 2, 4, 6 and 8 after BDC2.5 Dimethyl sulfoxide T cell transfer (day 0). Reagents were provided by UCB Celltech. Overt diabetes was

defined by two consecutive positive glucosuria tests and glycemia >200 mg/dL. Statistical analyses were performed with the nonparametric Mann–Whitney U test. The log-rank test was used for the comparison of diabetes incidence. The authors thank UCB Celltech for the generous gift of anti-IL-17 and isotype control reagents, L. Breton and the staff of the mouse facility for help in animal care and L. Ghazarian and J. Diana for critical reading of the manuscript. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale and the Centre National pour la Recherche Scientifique, grant from ANR-09-GENO-023 to A. L.. Anne-Sophie Gautron and Yannick Simoni were supported by doctoral fellowships from the Ministère de l’Education Nationale et de la Recherche et Technique and from Région Île-de-France. Conflict of interest: The authors declare no commercial or financial conflict of interest.

Most of the piglets seroconverted to PCV2 between 28 and 35 days post vaccination and, although not all the animals had seroconverted by the time of challenge, they were all protected against subsequent PCV2a challenge, suggesting that strong

PCV2 antibody responses are not entirely necessary for protection (39). IM administration of a live PCV1-2 vaccine has also been demonstrated to be effective in conventional (41) and in SPF pigs (42). Similarly, combined IM and intranasal administration of live PCV2 vaccine reduced PCV2 viremia and associated lesions after challenge in SPF pigs (40). In our study, the majority of IM vaccinated pigs (21/28) had seroconverted four weeks after vaccination, which is in agreement with previous studies (39, 40, 42). In contrast, among all the PO vaccinated pigs, only 1/28 pigs had seroconverted by four weeks post vaccination. The limited ability of the experimental live-attenuated PCV1-2 vaccine to induce a measurable systemic antibody https://www.selleckchem.com/products/Adriamycin.html response may be due to limited absorption and replication. Nevertheless, as evident from the PO-non-challenged

group, PCV2 antibodies continued to increase beyond 4 weeks, indicating a delayed antibody response with the PO route of vaccination. Development of mucosal immunity by assessing presence of locally secreted PCV2 specific antibodies (for example in fecal supernatants) was not investigated, but may have given further insights into the effectiveness of this route. In this study, PCV2 DNA in sera was detectable in all treatment groups challenged with PCV2b. This is in contrast GPCR Compound Library to previous studies where

PCV2 DNA was not detectable in vaccinated animals after challenge (39, 42). These conflicting results may Nutlin-3 solubility dmso be due to differences between studies in the detection methods for PCV2 DNA. For instance, the real-time PCR assay used in the current study is more sensitive than the gel-based PCR assay used previously (39). Other differences between studies include the utilization of a heterologous PCV2b challenge strain in the current study in contrast to a homologous PCV2a challenge strain used in a previous study (39). Significant differences in prevalence and amount of PCV2 DNA, with a reduction of the amount of PCV2 DNA in sera ranging from 79.2% to 84.6%, were found in pigs vaccinated IM compared to non-vaccinated pigs. Moreover, only 21.4% of pigs vaccinated by the IM route were PCV2 viremic after PCV2 challenge. Among the IM vaccinated pigs that had no detectable seroconversion prior to challenge, subsequent PCV2 viremia was not observed in 1/3 IM-PCV2-I pigs and in 3/3 IM-PCV2-PRRSV-CoI pigs, indicating evidence of protection and strengthening the importance of cellular immune response. The amount of PCV2 DNA in sera was also reduced in pigs vaccinated PO; however vaccine efficacy in the PO vaccinated groups as measured by decreased incidence and degree of viremia was not as impressive as that of the IM vaccinated groups.

Lymphatic reabsorption also may contribute to UFF, and we previously reported that lymphangiogenesis is linked to PF. But it is not clear yet whether lymphangiogenesis is a common finding in PF and peritonitis. Methods: We developed the two animal models: the rat chlorhexidine gluconate (CG) model and the rat methylglyoxal (MGO) model by intraperitoneal injections of CG or MGO solutions. We evaluated lymphatic vessel proliferation buy GDC-0068 and the expression of vascular endothelial growth factor (VEGF)-C and -D in their parietal peritoneum and diaphragm by immunohistochemistry (IHC) and real-time PCR. To analyze the lymphatic

function in the two models, we evaluated the amount of FITC in serum after intraperitoneal injection of FITC-dextran. Results: Both the CG model rats and the MGO model rats showed lymphangiognesis, which is more predominant in the diaphragm than in the parietal peritoneum. In the CG model, VEGF-C and -D expression were high in the diaphragm and the parietal peritoneum. On the other hand, VEGF-D expression was mainly upregulated in the diaphragm of the MGO model, while VEGF-C, and -D expression elavated in the parietal peritoneum. In the analysis of lymphatic function, we detected PI3K signaling pathway positive levels of FITC dextran in the serum of the rats, and found the level of FITC-dextran were extremely high in both models. Conclusion: Our

results suggest that Lymphangiogenesis is a common Oxymatrine feature of PF and peritonitis, which may contribute to UFF. CHAN SIU KIM, HO YIU WING, LAM CHI KWAN, TAM CHUN HEY, TANG WING CHUN ANTHONY, WONG SZE HO SUNNY Renal Unit, United Christian Hospital, Hong Kong Introduction: The emergence

of Extended Spectrum Betalactamase (ESBL) producing enterobacteriaceae imposed great challenge in treating CAPD peritonitis. There was in fact no generally agreed treatment strategy in this issue, especially on the drug of choice, route and frequency of administration. ISPD guideline update 2010 provided dosing recommendation of Intraperitoneal (IP) Imipenen/cilastatin. In an attempt to minimize Imipenem induced neurological complication, other carbapenem group antibiotics, most notably intraperitoneal Meropenem, has been tried successfully. However the pharmacokinetics, dosing and treatment outcome have not been well studied. In this report we retrospectively analyzed the treatment outcome by various treatment strategies. Methods: Renal registry of a single centre was retrieved for the period 1 Jan 2010 to 31 Dec 2013 and all the episodes of CAPD peritonitis caused by ESBL eneterobacteriaceae were studied. Data as shown in table 1 were collected. Outcome information displayed includes need of Tenckhoff catheter (T/C) removal, relapse of the same pathogen within 28 days of completing treatment and death.

Jα18 deficient mice, which specifically lack iNKT cells due to their inability to form the invariant TCRα

chain (12), are highly susceptible to S. pneumoniae infection, showing high bacterial counts in the lungs and a high mortality rate (11). Neutrophil numbers and the amount of chemokines/cytokines in the lungs are markedly lower in Jα18 deficient mice compared to wild type mice after intratracheal infection with S. pneumoniae (11). Furthermore, data suggest SRT1720 research buy that IFNγ derived from iNKT cells plays an important role in recruiting neutrophils to the lungs through increased production of MIP-2 and TNF by CD11bbright cells after S. pneumoniae infection (13) (Fig. 1). These results indicate that iNKT cells contribute to the clearance of S. pneumoniae by enhancing neutrophil recruitment to the lungs. Mouse iNKT cells are capable of inhibiting M. tuberculosis growth in macrophages in vitro (14). IFNγ derived

from iNKT cells stimulates M. tuberculosis infected macrophages to synthesize nitric oxide, which inhibits bacterial replication (14). IL-12 and IL-18 are both involved in this response. These data suggest that iNKT cells inhibit the growth of intracellular microbes by stimulating infected APCs (Fig. 2). It has previously been reported that mice deficient in CD1d, which lack both iNKT cells and NKT cells with diverse TCRs due to an inability of these MLN2238 price cells to differentiate in the thymus in the absence of CD1d (15–17), are not more susceptible to M. tuberculosis infection (18, 19). Similarly, Jα18 deficient mice are not more susceptible to M. tuberculosis infection (20, 21). However, in lethally irradiated Grape seed extract mice, adoptive transfer of iNKT cells decreases bacterial

numbers in the lungs following aerosol infection by M. tuberculosis (14), suggesting that iNKT cells inhibit the growth of this bacterium. Because CD1d expressing cells are found in granulomas of tuberculosis patients (22), iNKT cells may play a role in the response to M. tuberculosis in humans. Cryptococcus neoformans is a fungal pathogen that primarily infects the lungs, but it can disseminate to the central nervous system and cause meningitis in immunocompromised patients. iNKT cells have been shown to accumulate in the lungs in the early phase (day 3 post-infection) of C. neoformans infection in a CCL-2 (MCP-1) dependent manner (23). Jα18 deficient mice show a significantly attenuated Th1 response (23), and Th1 is a critical component of the response to C. neoformans. Consistent with this, Jα18 deficient mice take longer to clear C. neoformans from their lungs than do wild type mice (23). These data suggest that iNKT cells contribute to the development of an effective Th1 response to C. neoformans.

The maximum change in fluorescence over baseline was quantified using softmax pro (version 5) software (Molecular Devices). The chemotaxis assay was performed using a 48-well chemotaxis micro-chamber (Neuroprobe, Cabin John, MD). Mast cells (50 μl of 3 × 106 cells/ml) were added to the upper wells separated from the lower wells containing chemoattractants by a polycarbonate membrane with pores 8 μm in diameter. After 3 hr of incubation, the mast cells that migrated and adhered to the underside of the filter were fixed and stained with DiffQuick. The membrane was mounted,

and the cells that migrated were counted under a light microscope in three randomly chosen high-power fields. In some experiments, inhibitors were added

2 hr before the assay, and chemotaxis was evaluated as described above. Mast cells (1 × 106 this website cells) were suspended in BD Cytofix/Cytoperm solution (BD Biosciences Pharmingen, San Diego, CA) for 20 min according to the manufacturer’s instructions. Following one wash with BD Perm/Wash buffer, an antibody against the α7 nAChR (Santa Cruz Biotechnology, Santa Cruz, CA) Idelalisib mw or an isotype control rat IgG1κ antibody (BD Biosciences) was added for 30 min. The expression of the α7 nAChR was evaluated by FACS after staining with FITC-conjugated goat anti-rat IgG (BD Biosciences). Mast cells (100 μl at a density of 3 × 107 cells/ml) were transfected with 400 nmα7 nAChR siRNA or control siRNA (Applied check Biosystems) using the Amaxa Cell Line Nucleofector Kit V, programme T-030 (Lonza Bio, Cologne, Germany), according to the manufacturer’s instructions. Gene silencing was carried out for at least 24 hr, and the efficacy of knockdown was confirmed by quantitative real-time PCR using α7 nAChR-specific primers/probes. Following transfection, the cells were stimulated with catestatin peptides, and an assessment of degranulation or cytokine/chemokine production was carried out as described above. Statistical analysis was performed using one-way analysis of variance with a multiple

comparison test or Student’s t-test (Prism 4; GraphPad Software, San Diego, CA), and P < 0·05 was considered to be significant. The results are shown as the mean ± SD. The β-hexosaminidase enzyme is released in combination with histamine and, therefore, is a marker of mast cell degranulation.20 As shown in Fig. 1(a), wild-type catestatin and its variants markedly induced β-hexosaminidase release from LAD2 cells at 2·5 μm, whereas nanomolar concentrations (100 and 500 nm) did not cause mast cell degranulation. Wild-type catestatin, Gly364Ser and Pro370Leu displayed nearly identical potencies, whereas Arg374Gln showed lower activity. Scrambled catestatin used as a control peptide had no effect on mast cell degranulation, suggesting that catestatin-mediated human mast cell activation is specific.

Aberrant mitochondrial morphology may impact on endoplasmic

reticulum/mitochondria calcium transfer mediated by Mfn2 [96], and endoplasmic reticulum stress reported in mSOD1 models may also damage this important calcium buffering process [97,98]. In addition to the functional deficits that mitochondria endure in ALS, their intrinsic role in the apoptotic cascade may be an import factor. In ALS patients, biochemical markers indicative of apoptosis have https://www.selleckchem.com/screening/mapk-library.html been noted at the terminal stage of disease [99–102]. Additionally, co-immunoprecipitation experiments in both SALS and FALS patients have indicated that, compared to control levels, pro-apoptotic Bax dimerization is enhanced in the motor cortex, and the protective selleck Bax-Bcl-2 interaction is decreased [103]. Accordingly, sequential activation of caspases has been observed in both mSOD1 transfected neuronal cell lines and G85R mSOD1 mice [65,100,104]. The initiation of apoptosis may arise secondary to mSOD1-induced mitochondrial dysfunction, either linked to impairment of the ETC, reduced calcium buffering, or as a direct consequence of mSOD1 localization. For example, it has been noted that Bcl-2 is sequestered in the mSOD1 mitochondrial aggregates seen in FALS [65]. Studies in neuroblastoma cells demonstrated that the apoptosis-inducing ability of mSOD1 is linked to its aggregation state,

with the formation of mSOD1 inclusions rendering NSC-34 cells vulnerable to apoptosis upon oxidative stress, via capsase 3 activation, and the presence of dispersed mSOD1 protecting against this fate [105]. However, controversy surrounds the importance of apoptosis in neuronal degeneration in ALS. mSOD1 transgenic mice lacking the upstream regulator of caspase

1, caspase 11, failed to show any improvement in the disease phenotype [106], challenging the relevance of the observation of early activation of caspase 1 in mSOD1 G85R mice [65]. Additionally, morphological and biochemical markers of apoptotic cell death, such as terminal deoxynucleotide transferase dUTP nick end labelling staining, are scarce, both in ALS patients and disease [107]. The concept of ALS as a dying back neuropathy has arisen, with local toxicity Amine dehydrogenase resulting from the dysfunctional mitochondria inducing damage to the distal axon. Although insufficient to kill the neurone and focal enough to avoid detection with most biochemical markers, the cumulative defects could eventually spread to the cell body. This hypothesis, although speculative, specifically correlates with denervation at the neuromuscular junction [53,108]. Abnormalities in the morphology of mitochondria were initially recognized in ALS autopsy specimens, with subsarcolemmal aggregates of mitochondria seen in skeletal muscle [47].

Furthermore, while ATRAP-TG showed an inhibition of the Ang II-mediated increase in α subunit of epithelial sodium channel (αENaC) expression, ATRAP-KO exhibited an enhancement of the Ang II-mediated increase in αENaC expression, compared with WT. Conclusion: These results indicate MDV3100 research buy that ATRAP can inhibit the development of hypertension via modulation of renal tubule electrolyte transporter /urine sodium excretion system under Ang II infusion. Collectively, while ATRAP, with a high endogenous expression in renal tubules, preserves baseline physiological AT1R signaling activity, it would suppress pathological overactivation

of AT1R signaling under pathological conditions. HINAMOTO NORIKAZU1, MAESHIMA YOHEI2, YAMASAKI HIROKO1, WATATANI HIROYUKI1, UJIKE HARUYO1, TANABE KATSUYUKI1, MASUDA KANA1, SUGIYAMA HITOSHI3, SATO YASUFUMI4, MAKINO HIROFUMI1 1Dept. of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Dept. of Chronic Kidney Disease and Cardiovascular disease, Okayama University Graduate Abiraterone School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 3Center for Chronic Kidney Disease and Peritoneal Dialysis, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical

Sciences, Okayama, Japan; 4Dept. of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku Univ., Sendai, Japan Introduction: Hypertensive nephrosclerosis is one of the major pathogenic disorders predisposing ESRD. Angiotensin-II (A-II) infusion induces hypertension and glomerular as well as focal renal tubulointerstitial injuries in experimental animal models. We recently reported the protective role of Vasohibin-1(VASH1), a negative feedback Demeclocycline regulator of angiogenesis, in diabetic nephropathy, but its role on hypertensive nephrosclerosis remains to be elucidated. In the present study, we aimed to evaluate the role of endogenous VASH1 in regulating renal alterations in an A-II-infused

hypertension model. Methods: Male VASH1+/− or wild-type (VASH1+/+) littermates (C57/BL6J background) received continuous infusion of saline or A-II (1000 ng/kg/min) via osmotic minipumps. Mice were sacrificed on Day 28 and the kidneys were obtained. Morphometric analysis, immunohistochemistry and real-time PCR were performed. Results: Hypertension was observed in the A-II-infused animals, and blood pressure was not significantly different between A-II-infused wild-type and VASH1+/− mice. A-II-induced increase of proteinuria, glomerular volume, mesangial matrix index (assessed by the computer-image analysis) and glomerular nephrin redistribution index were significantly exacerbated in the VASH1+/− mice compared with the VASH1+/+ mice.

[16] CD4+ T cells labelled with CFSE were cultured with anti-CD3 antibody (0·5 μg/ml) selleckchem for 48 or 72 hr (Fig. 2f). At each time-point examined, SD-4+/+ and SD-4−/− T cells showed almost identical patterns of cell division (as reflected from diffusion of CFSE fluorescent intensity).

Similar results were also noted with lower concentrations (0·1 and 0·3 μg/ml) of anti-CD3 antibody (see Supplementary material, Fig. S2). We then examined the effect of SD-4 deletion on the intrinsic response triggered by concanavalin A, wihch activates T cells in a non-specific manner (Fig. 2g). Again, there was no significant change in T-cell proliferation. Hence, lack of SD-4 expression does not alter the intrinsic responsiveness of T cells to TCR-dependent or non-specific Alvelestat stimulation. These features distinguish SD-4 from PD-1 and BTLA, whose respective deletions augment T-cell responses to anti-CD3 stimulation.[20, 21] Using the mixed lymphocyte reaction, we examined the impact of SD-4 deletion on T-cell reactivity in response to allogeneic DC-HIL+ APC (Fig. 3a,b). CD4+ T cells

(varying numbers) isolated from WT or KO C57BL/6 mice were co-cultured with DC (constant number) prepared from BM cells of BALB/c mice. T-cell activation was measured by secreted IL-2 (Fig. 3a) or by proliferation (Fig. 3b). SD-4−/− T cells produced IL-2 at a four-fold greater level and proliferated at a two-fold higher level, respectively, than SD-4+/+ T cells. We next used a defined antigen model of gp100 (melanoma-associated antigen).[22] SD-4 gene deficiency was introduced into the pmel-1 TCR transgenic mice (in which all CD8+ T cells express the same TCR specific to a particular gp100 antigen peptide).[23] With respect to relative proportions of leucocyte sub-populations in lymphoid organs, there was no significant difference between SD-4+/+ and SD-4−/− pmel-1 mice (data not shown). We then assayed the reactivity of T cells to gp100 peptide-loaded APC. Spleen cells isolated from SD-4+/+ or SD-4−/− pmel-1 mice were

stimulated by increasing doses of antigen and measured for proliferation (Fig. 3c). SD-4+/+ pmel-1 spleen cells proliferated and produced IL-2 in response to gp100 antigen in a dose-dependent manner. Similarly, SD-4−/− pmel-1 spleen cells Nintedanib (BIBF 1120) responded to antigen, but with significantly elevated levels (more than twofold greater responses by SD-4−/− pmel-1 T cells) at almost every single dose of antigen. To more rigorously examine the impact of SD-4 deletion, BMDC were prepared from WT mice and allowed to stimulate SD-4+/+ or SD-4−/− CD8+ T cells (Fig. 3d). SD-4−/− CD8+ T cells produced greater levels of IL-2 than SD-4+/+ CD8+ T cells (up to twofold), consistent with the previous data (Fig. 3c). As SD-4 is also expressed by DC (unpublished data), we examined the possibility that contaminant APC in the T-cell preparation from KO mice contributed to hyperactivation (Fig. 3a).

Further comparison of thyroid function in patients with different genotypes showed that the frequency of the G-allele was significantly higher among hypothyroid patients (P < 0·05). Interestingly, among 25 hypothyroid patients U0126 with both elevated thyroid peroxidase antibody and thyroglobulin antibody concentrations, 14 presented with the AG genotype and 11 with the GG genotype, while no AA genotype was found in this group. Evaluating the independent effect of different genetic and non-genetic factors on thyroid function with multiple regression analysis, we established a strong contribution

of thyroid peroxidase antibodies (P < 0·0002) and an insignificant contribution of thyroglobulin antibodies, CT60 genotype, age, family history and smoking. After elimination of the thyroid autoantibody effect, the contribution of the CT60 genotype reached the level of significance (P < 0·05). This study of patients with two different forms of thyroid

autoimmune disease, HT and PPT, demonstrates a strong contribution of CT60 CTLA-4 SNP to thyroid autoantibody production. The significant increase of thyroid peroxidase antibody concentration and slight increase of thyroglobulin antibody concentration found in patients carrying the polymorphous CT60 CTLA-4 allele is consistent with our previous report on HT patients, where exon 1 and promoter CTLA-4 polymorphisms were studied [6]. Exon 1 SNP has also been shown to influence higher thyroid AZD2014 order autoantibody production in Graves’ disease [9]. Nevertheless, no data are available in the literature on association of Leukocyte receptor tyrosine kinase CT60 SNP with thyroid autoantibody production. Similarly, the data on genetic susceptibility in PPT are scarce in spite of the relatively high prevalence of 8% in the postpartum period [10]. A few earlier reports suggested an association with human leucocyte antigen (HLA) status, which was not confirmed afterwards [11]. The first report referring to the CTLA-4 gene in PPT

was published a decade ago, describing no association between PPT and microsatellite CTLA-4 polymorphism [12]. The second report was our recent case–control study, where we were not able to demonstrate a link between CT60 CTLA-4 SNP and PPT [13]. However, the strong influence of thyroid peroxidase antibodies on development, thyroid function and prognosis of PPT was reported, as patients with higher thyroid peroxidase antibodies in the postpartum period developed PPT more often, presented with hypothyroidism more often and developed permanent hypothyroidism more often [2,11,14,15]. The current study also showed that thyroid peroxidase antibody concentrations were significantly higher in the hypothyroid form of PPT and the frequency of patients positive for thyroid autoantibodies was also significantly higher among hypothyroid patients.

Nakashima et al.[48] showed the accumulation of IL-17+ T cells in the deciduas in women selleck products with inevitable abortion. Decidual IL-17+ T cells were mostly CD4+ T cells and a few CD8+ cells also expressed IL-17 in this study. In addition, the number of decidual IL-17+ cells was positively correlated with the number of decidual neutrophils. However, they could not find any difference in the number of decidual IL-17+ T cells between women with missed abortion and normal pregnancy. From these results, the authors concluded that decidual IL-17+ cells might be involved in the inflammation of the late stage of abortive process, not the causative factor of abortion.[48] Because their data of IL-17+

cells were limited to inevitable abortion, not to RPL, it may be difficult to generalize the results as the immunologic mechanism of RPL. A series of studies concerning Th17 cells have been reported regarding RPL in the past 2 years. Wang et al.[70] found an increase in Th17 cells in the peripheral blood and decidua of women with unexplained RPL as compared to normal pregnant women. Serum IL-17 and IL-23 levels were significantly higher in women with RPL. Furthermore, Th17-related this website molecules such as IL-17, IL-23, and retinoid orphan receptor C (RORC) were significantly expressed in the deciduas of women with RPL. The number of Th17 cells inversely correlated

with that of regulatory T cells in the peripheral blood and deciduas. The same group has reported another Th17 cell study in women with RPL.[73] They found that the proportions of peripheral blood CCR6+ CD4+ T and CCR6+ IL17+ T cells were significantly

elevated in women with RPL as compared to healthy pregnant women undergoing elective abortion. In ex vivo culture study, IL-17 production from CD4+ T cells was significantly higher for in women with RPL and regulatory T cells from women with RPL were less suppressive to the expression of IL-17 as compared to control women. Similarly, a decrease in CD4+ CD25bright Foxp3+ regulatory T cells and increase in Th17 cells have been reported in the peripheral blood of women with RPL in comparison with normal healthy pregnant women.[64] The ratio of Th17/regulatory T cells was significantly increased in women with RPL as compared to normal pregnant and non-pregnant women. The proportion of regulatory T cells negatively correlated with the proportion of Th17 cells (Table 1). Serum IL-17 levels correlated positively with Th17 cells and the ratio of Th17/regulatory T cells.[64] These results suggest that regulatory T cells inhibit IL-17 expression and suppressive function of regulatory T cells on Th17 cells may decrease in women with RPL. Our group recently published a study that investigated pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-17), anti-inflammatory cytokine IL-10, and Foxp3 in the PBMCs of idiopathic women with RPL.