IgE-expressing long-lived plasma cells in persistent sensitization

Persistent allergies affect the quality of life of patients and increase economic burdens. Many clinical observations indicate the presence of IgE+ long-lived plasma cells (LLPCs), which account for the persistent secretion of specific IgE; however, the characteristics of the IgE+ LLPCs have yet to be identified clearly. In this review, we summarized the generation of IgE+ PCs, discussed the prosurvival factors in the microenvironment, and reviewed the unique IgE-BCR signaling, which may bring insights into understanding the survival mechanisms of IgE+ LLPCs

Tissue-Specific Education of Decidual NK Cells.

During human pregnancy, fetal trophoblast cells invade the decidua and remodel maternal spiral arteries to establish adequate nutrition during gestation. Tissue NK cells in the decidua (dNK) express inhibitory NK receptors (iNKR) that recognize allogeneic HLA-C molecules on trophoblast. Where this results in excessive dNK inhibition, the risk of pre-eclampsia or growth restriction is increased. However, the role of maternal, self-HLA-C in regulating dNK responsiveness is unknown. We investigated how the expression and function of five iNKR in dNK is influenced by maternal HLA-C. In dNK isolated from women who have HLA-C alleles that carry a C2 epitope, there is decreased expression frequency of the cognate receptor, KIR2DL1. In contrast, women with HLA-C alleles bearing a C1 epitope have increased frequency of the corresponding receptor, KIR2DL3. Maternal HLA-C had no significant effect on KIR2DL1 or KIR2DL3 in peripheral blood NK cells (pbNK). This resulted in a very different KIR repertoire for dNK capable of binding C1 or C2 epitopes compared with pbNK. We also show that, although maternal KIR2DL1 binding to C2 epitope educates dNK cells to acquire functional competence, the effects of other iNKR on dNK responsiveness are quite different from those in pbNK. This provides a basis for understanding how dNK responses to allogeneic trophoblast affect the outcome of pregnancy. Our findings suggest that the mechanisms that determine the repertoire of iNKR and the effect of self-MHC on NK education may differ in tissue NK cells compared with pbNK.This work was supported by Wellcome Trust Grants 090108/Z/09/Z and 085992/Z/08/Z, as well as by British Heart Foundation Grant PG/09/077/27964. P.R.K. was the recipient of a Wellcome Trust Ph.D. studentship.This is the final version of the article. It first appeared from the American Association of Immunologists via http://dx.doi.org/10.4049/​jimmunol.150122

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Material parameter modeling and solution technique using birth–death element for notched metallic panel repaired with bonded composite patch

AbstractThis paper seeks to outline a novel three-layer model and a new birth–death element solution technique to evaluate static strength of notched metallic panel repaired with bonded composite patch and to optimize material parameters. The higher order 3D, 8-node isotropic solid element and 8-node anisotropic layered solid element with three degrees of freedom per node are respectively implemented to model substrate panel, adhesive layer and composite patch to establish three-layer model of repaired panel. The new solving technique based on birth–death element is developed to allow solution of the stress pattern of repaired panel for identifying failure mode. The new model and its solution are used to model failure mode and residual strength of repaired panel, and the obtained results have a good agreement with the experimental findings. Finally, the influences of material parameter of adhesive layer and composite patch on the residual strength of repaired panel are investigated for optimizing material properties to meet operational and environmental constraints

Wogonin Suppresses IL-10 Production in B Cells via STAT3 and ERK Signaling Pathway

Wogonin (5,7-dihydroxy-8-methoxyflavone) is an ingredient of the extracts from Scutellaria baicalensis, which has documented a wide spectrum of anti-inflammatory and antitumor activities, including inhibiting regulatory T cells, regulating effector T cell functions, and mediating macrophage immunity. However, the potential effect of Wogonin on B cells has not been fully understood. Here, our results showed that Wogonin inhibited IL-10 secretion in B cells. When purified B cells were activated by lipopolysaccharide (LPS) in vitro, the amount of IL-10 production in supernatant was decreased by Wogonin significantly. The protective role of B cells on dextran sulfate sodium- (DSS-) induced colitis was alleviated after exposure to Wogonin. Furthermore, administration of Wogonin on LPS-treated B cells suppressed phosphorylation of STAT3 and ERK, but not AKT. Interestingly, among those IL-10 signaling-associated transcription factors, mRNA and protein levels of Hif-1α were specifically decreased by Wogonin. Overall, our study indicates that Wogonin suppresses potentially IL-10 production in B cells via inhibition of the STAT3 and ERK signaling pathway as well as inhibition of mRNA and protein levels of the transcription factor Hif-1α. These results provide novel and potential molecular targets of Wogonin in B cells and help us further understand its mechanism of action, which could potentially improve its clinical application in the future

The implications of accession

Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinom

[Barco de Arena, par la Compagnie Leandre et Claire. Chalon dans la Rue. 2008 / photographies de Joël Verhoustraeten]

Additional file 5: Table S1. Clinicopathological characteristics of cervical carcinoma patient samples

DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1

Background: Several studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear. Methods: DDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed. Results: DDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells. Conclusions: Our findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC

MOESM3 of High brain acid soluble protein 1(BASP1) is a poor prognostic factor for cervical cancer and promotes tumor growth

Additional file 3: Figure S1. Knockdown of BASP1 inhibited the proliferation of cervical cancer. (A) MTT assay showing the effect of BASP1 knockdown on cell proliferation. (B) Colony formation assay showing the effect of BASP1 knockdown on cell proliferation, Representative micrographs (left) and quantification (right) of crystal violet stained cell colonies. (C) Cell cycle analysis indicating the effect of BASP1 knockdown on cell proliferation. *p < 0.05, error bars represent mean ± SD