32 research outputs found

    Importance of EMT Factor ZEB1 in cDC1 “MutuDC Line” Mediated Induction of Th1 Immune Response

    Get PDF
    The role of Epithelial to Mesenchymal Transition (EMT) factor Zeb1 is well defined in metastasis and cancer progression but it's importance in dendritic cells (DCs) is unexplored until now. For the first time we report here that Zeb1 controls immunogenic responses of CD8α+ conventional Type-I (cDC1) DCs. We found that ZEB1 expression increases significantly after TLR9 stimulation and its depletion impairs activation, co-stimulation and secretion of important cytokines like IL-6, IL-10 and IL-12 in cDC1 MutuDC line. We further confirmed our findings in primary cDC1 DCs derived from bone marrow. Co-culture of these Zeb1 knock down (KD) DCs with OT-II CD4+ T helper cells skewed their differentiation toward Th2 subtype. Moreover, adoptive transfer of activated Zeb1 KD DCs cleared intestinal worms in helminth infected mice by increasing Th2 responses in vivo. Integrative genomic analysis showed Zeb1 as an activator of immune response genes in cDC1 MutuDCs as compared to other pathway genes. In addition, differentially regulated genes in Zeb1 KD RNA-seq showed significant enrichment of Th2 activation pathways supporting our in vitro findings. Mechanistically, we showed that decreased IL-12 secreted by Zeb1 KD DCs is the plausible mechanism for increased Th2 differentiation. Collectively our data demonstrate that Zeb1 could be targeted in DCs to modulate T-cell mediated adaptive immune responses

    QlicRice: a web interface for abiotic stress responsive QTL and loci interaction channels in rice

    Get PDF
    The QlicRice database is designed to host publicly accessible, abiotic stress responsive quantitative trait loci (QTLs) in rice (Oryza sativa) and their corresponding sequenced gene loci. It provides a platform for the data mining of abiotic stress responsive QTLs, as well as browsing and annotating associated traits, their location on a sequenced genome, mapped expressed sequence tags (ESTs) and tissue and growth stage-specific expressions on the whole genome. Information on QTLs related to abiotic stresses and their corresponding loci from a genomic perspective has not yet been integrated on an accessible, user-friendly platform. QlicRice offers client-responsive architecture to retrieve meaningful biological information—integrated and named ‘Qlic Search’—embedded in a query phrase autocomplete feature, coupled with multiple search options that include trait names, genes and QTL IDs. A comprehensive physical and genetic map and vital statistics have been provided in a graphical manner for deciphering the position of QTLs on different chromosomes. A convenient and intuitive user interface have been designed to help users retrieve associations to agronomically important QTLs on abiotic stress response in rice

    EMT factor Zeb1 depletion in dendritic cells enhances Helminth clearance in mice by increasing Th2 cell differentiation

    No full text
    Dendritic cells are professional antigen presenting cells that act as bridging link between innate and adaptive immune system. They are equipped with pathogen recognition receptors (PRR) to identify the pathogen associated molecular pattern (PAMPS) on any antigen. DCs elicit an immune response through polarizing T cells towards various subtypes like Th1, Th2 & Tregs. Though DC-T cell interaction has been widely studied, but how this single DC molecule amalgamate various transcriptional signals for translating the message to the T cells and induce diverse immunological responses still needs to be unraveled. Therefore to identify the role of transcription factor in immune programming we have targeted the largest member of TFs family, Zinc Finger Transcription Factors (ZF-TFs). Among various ZF-TFs we have narrowed our study to three interesting candidates Zeb1, Zeb2 and Zbtb10 based on their expression in DCs from an unpublished microarray data. Here in this study we have tried to understand the role of Zeb1, master regulator of EMT program in orchestrating DC responses. Zeb1 links the epithelial – mesenchymal transition and has been widely studied molecule in cancer biology. Except for the fact that it act as transcriptional repressor and represses IL2 gene promoter no other reports are available in immune biology, thereby rendering it a perfect candidate to be used for detailed characterization in dendritic cells. In our study, we found that Zeb1 depleted CD8α+DCs shows an increase in co-stimulatory marker like CD80 & CD86 whereas there is a decrease in MHC class I & II molecule. Thereafter at transcript & protein level we found decrease in pro-inflammatory & anti-inflammatory cytokine like IL6 & IL10 respectively, the bioactive form of IL12 i.e. IL12p70 which polarizes T cells towards Th1 response showed a significant decrease in bio-plex when compared with control CD8α+DCs. The regulatory markers which develop regulatory T cells like Pdl1, IL27 also showed decreasing trend in zeb1 depleted DCs. Thereafter we speculated that these Zeb1 perturbed DCs might be involved in default Th2 program. So, we looked into T-cell polarization by co-culture & MLR experiments which showed an increase in GATA3+ T cells, a signature transcription factor for Th2 subtype along with higher levels of IL4, IL5 and IL13 Th2 cytokines. To evaluate the in-vivo function of Zeb1 knockdown (KD) cells we developed Helminth Polygyrus (H.Poly) disease model in mice, there we assessed for the worm load in intestine and egg count in the feces which showed a marked decrease in worm count and egg count in Zeb1 KD adoptive transfer mice as compared to control mice. The T cell response was examined through the draining lymph node (mesenteric lymph node) where we found significant increase in GATA3+ T cells along with IL5 and IL13; this suggested that Zeb1 KD DCs polarize the T cells towards Th2 response which results in clearance of H. polygyrus in mice

    Direct LPS recognition and activation of CD8+T cells via TLR4 in patients with rheumatoid arthritis

    No full text
    Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by abnormal immune responses to self-antigens. Though the pathogenesis of RA is not yet fully elucidated, it is known to be induced by environmental factors on a genetically susceptible background. Toll-like Receptors (TLRs) have been established to recognize specific patterns of microbial components and lead to systemic immune responses in Rheumatoid arthritis (RA). TLRs are expressed by cells in inflamed joints of RA patients and variety of endogenous TLR ligands is present within those joints. This study suggests that the over expression of TLR4 in CD8+T cells from RA patients may contribute to the abnormal immune activation of pro inflammatory cytokines and enhance the acute inflammation. Methods: Eighty seven RA patients and 70 healthy donors participated in this study. Clinical variations like disease duration, number of actively inflamed joints, number, and type of bones deformities, CRP, RF, Anti-CCP, ESR (Erythrocyte Sedimentation Rate), and therapeutic interventions were recorded for each patient and DAS 28 scores were calculated with the help of the clinician. We analyzed the expression of TLR4 in transcript level by real-time PCR and protein level by flow cytometry in CD8+T cells of RA patients. Different cytokines level was checked after stimulation of CD8+T cells in TLR4 agonist. We have checked the MAP Kinase – ERK signal transduction in CD8+Tcells. Results: A significant increase of TLR4 in both transcript level and protein level in patients with RA compared to healthy donors. We got a strong positive correlation between TLR4 expression and DAS 28 score. The ROC curve analysis confirmed the significance of TLR4 expression in RA patients. We found that TLR4 ligand responsiveness significantly increased the expression of different inflammatory mediators in purified CD8+T cells of RA patients compared with healthy individuals after in vitro stimulation. Our result showed TLR4 stimulation induces ERK phosphorylation in CD8+T cells. Conclusion: In summary, our data suggest an increased expression of TLR4 in CD8+T cells play a major role in inflammation of RA patients

    Not Available

    No full text
    Not AvailableNBackground Transcription factors (TFs) and microRNAs (miRNAs) are primary gene regulators within the cell. Regulatory mechanisms of these two main regulators are of great interest to biologists and may provide insights into the abiotic and biotic stresses. However, the interaction between miRNAs and TFs in a gene regulatory network (GRN) still remains uncovered. Previous research has been mostly directed at inferring either miRNA or TF regulatory networks from data. However, networks involving a single type of regulator may not fully reveal the complex gene regulatory mechanisms, therefore study of interplay among these two regulators in gene regulation is important towards explaining the mechanism of different abiotic stresses.Not Availabl
    corecore