BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation.

The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that regulates inflammatory responses downstream of TLR signaling. Here we find that BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to regulate T helper (Th) 17 and Th1 cell differentiation, respectively.

MyD88 Signaling in T Cells Is Critical for Effector CD4 T Cell Differentiation following a Transitional T Follicular Helper Cell Stage.

Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive T follicular helper (Tfh) lineage cell development remain unclear.

Monoclonal Antibodies against Circumsporozoite Protein.

Malaria is a mosquito-borne infectious disease caused by the parasite spp. Malaria continues to have a devastating impact on human health. Sporozoites are the infective forms of the parasite inside mosquito salivary glands.

ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination.

Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) sense microbial ligands and initiate signaling to induce inflammatory responses. Although the quality of inflammatory responses is influenced by internalization of TLRs, the role of endosomal maturation in clearing receptors and terminating inflammatory responses is not well understood. Here, we report that Drosophila and mammalian Vps33B proteins play critical roles in the maturation of phagosomes and endosomes following microbial recognition.

Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation.

Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation, a process involving up-regulation of MHC and costimulatory molecules and secretion of proinflammatory cytokines. All TLRs except TLR3 achieve these outcomes by using the signaling adaptor myeloid differentiation factor 88. TLR4 and TLR3 can both use the Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway leading to IFN regulatory factor 3 (IRF3) activation and induction of IFN-β and -α4.

Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo.

TLR activation on dendritic cells (DCs) induces DC maturation and secretion of proinflammatory cytokines, both of which are important for activation and differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T cell responses is less clear. In this study, we tested the ability of different TLRs to regulate CD8 T cell responses to pathogens.

Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors.

Dendritic cells (DCs) function as professional antigen presenting cells and are critical for linking innate immune responses to the induction of adaptive immunity. Many current cancer DC vaccine strategies rely on differentiating DCs, feeding them tumor antigens ex vivo, and infusing them into patients. Importantly, this strategy relies on prior knowledge of suitable “tumor-specific” antigens to prime an effective anti-tumor response.

Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation.

Background: It has been shown that human immunodeficiency virus (HIV)-1 infection induces the production of endogenous lipids required for effective viral production, and the cluster of differentiation (CD)1 molecule CD1d is downregulated by HIV-1 infection. However, the role of endogenous lipid presentation and the implications of CD1 downregulation by HIV-1 infection have not yet been characterized.

Results: In this study, we observed downregulation of both CD1c and CD1d expression through a Vpu-dependent and Nef-independent mechanism, and the concomitant HIV-1-induced production of host cholesterol decreased the extent of CD1c and CD1d modulation.

Cultured cerebellar granule neurons as an in vitro aging model: topoisomerase IIβ as an additional biomarker in DNA repair and aging.

Aging in the brain is a multicellular process manifesting as neurodegeneration and associated functional impairment. In the present study, we report that cerebellar granule neurons (CGNs) in culture show senescence-mediated molecular changes indicating establishment of aging processes in vitro. CGNs were viable for 5 weeks followed by cellular degeneration.

An efficient targeted drug delivery through apotransferrin loaded nanoparticles.

Background: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules.

Distinct roles of Topoisomerase II isoforms: DNA damage accelerating alpha, double strand break repair promoting beta.

Topoisomerase II alpha (TopoIIalpha) and Topoisomerase II beta (TopoIIbeta) isoforms are different gene products having conserved catalytic activities. The alpha isoform is present in proliferating cell, while beta isoform is predominantly present in non-proliferating cells namely neurons suggesting its role in non-replicating functions of DNA. The functions of TopoIIalpha and TopoIIbeta isoforms are analyzed in peroxide-mediated DNA damage and double strand breaks (DSBs) repair in neuroblastoma and astrocytoma cells.

Regulation of topoisomerase II alpha and beta in HIV-1 infected and uninfected neuroblastoma and astrocytoma cells: involvement of distinct nordihydroguaretic acid sensitive inflammatory pathways.

The activity of Topoisomerase II alpha and beta isoforms is tightly regulated during different phases of cell cycle. In the present study, the action of anti-inflammatory agents, nordihydroguaretic acid (NDGA) is analyzed in HIV-1 infected CXCR4(+), CCR5(+) and CD4(-) SK-N-SH neuroblastoma, CXCR4(+), CCR5(+) and CD4(-) 1321N1 astrocytoma and CXCR4(+), CCR5(+/-) and CD4(-) GO-G-CCM glioblastoma cell lines. In SK-N-SH and 1321N1 the expression of Topoisomerase II alpha is concomitant with that of LOX-5 and is highly sensitive to NDGA, while the Topoisomerase II beta is expressed along with TNFalpha and exhibits low sensitivity to NDGA, suggesting distinct pathways of regulation for the two isoforms.

Analysis of age dependent changes of Topoisomerase II alpha and beta in rat brain.

Eukaryotic Topoisomerase II (Topo II) is present in two isoforms alpha and beta. The alpha isoform is predominantly localized in proliferative tissue, while beta isoform is present in all tissues. In the present study we report the activity and protein levels of Topoisomerase II alpha and beta in rat brains of different age groups viz.