HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity.

is the most common cause of fungal infections in humans, and disseminated candidiasis has become one of the leading causes of hospital-acquired bloodstream infections with a high mortality rate. However, little is known about the host-pathogen interactions and the mechanisms of antifungal immunity. Here, we report that Nedd4 (neuronal precursor cell-expressed developmentally downregulated 4) is essential for signaling through Dectin-1 and Dectin-2/3.

Distinct roles for Blimp-1 in autoreactive CD4 T cells during priming and effector phase of autoimmune encephalomyelitis.

B lymphocyte-induced maturation protein (Blimp-1) is a transcription factor that regulates effector/memory B cells and CD8 T cells. Here we show that Blimp-1 is expressed in both Th1 and Th17 cells in vitro and highly expressed in effector/memory myelin-specific CD4 T cells in experimental autoimmune encephalomyelitis (EAE) mice. The immunized Blimp-1 conditional knockout mice have a significantly delayed disease onset but enhanced disease severity during the effector phase compared to their wild-type littermates, suggesting that Blimp-1 is a unique transcription factor with distinct roles in the regulation of myelin-specific CD4 T cells during priming and effector phase of EAE.

Regulation of effector function of CNS autoreactive CD4 T cells through inhibitory receptors and IL-7Rα.

Background: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity.

Roles for SUMO in pre-mRNA processing.

When the small ubiquitin-like modifier (SUMO)-1 protein is localized on the genome, it is found on proteins bound to the promoters of the most highly active genes and on proteins bound to the DNA-encoding exons. Inhibition of the SUMO-1 modification leads to reductions in initiation of messenger RNA (mRNA) synthesis and splicing. In this review, we discuss what is known about the SUMOylation of factors involved in transcription initiation, pre-mRNA processing, and polyadenylation.

Expression dynamics of Toll-like receptors mRNA and cytokines in porcine peripheral blood mononuclear cells stimulated by bacterial lipopolysaccharide.

The Toll-like receptor (TLR)4 is critical for the recognition of Gram-negative bacterial lipopolysaccharide (LPS) but in porcine peripheral blood mononuclear cells (PBMCs) it may cooperate with other TLRs and lead to the production of inflammatory cytokines. Therefore, we analyzed TLR1-10 mRNA expression in porcine PBMCs stimulated with LPS over time (1-48 h) by using quantitative real-time PCR and cytokine proteins level by ELISA in culture supernatant. TLR1-10 mRNA was detectable in porcine PBMCs.