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T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3-5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of(More)
B cells are important effectors and regulators of adaptive and innate immune responses, inflammation and autoimmunity, for instance in anti-NMDA-receptor (NMDAR) encephalitis. Thus, pharmacological modulation of B-cell function could be an effective regimen in therapeutic strategies. Since the non-competitive NMDAR antagonist memantine is clinically applied(More)
Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a(More)
N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that play an important role in neuronal development, plasticity, and excitotoxicity. NMDAR antagonists are neuroprotective in animal models of neuronal diseases, and the NMDAR open-channel blocker memantine is used to treat Alzheimer's disease. In view of the clinical application of these(More)
By studying mice in which the Nfatc1 gene was inactivated in bone marrow, spleen, or germinal center B cells, we show that NFATc1 supports the proliferation and suppresses the activation-induced cell death of splenic B cells upon B cell receptor (BCR) stimulation. BCR triggering leads to expression of NFATc1/αA, a short isoform of NFATc1, in splenic B(More)
The signals that direct differentiation of T cells to the CD4 or CD8 lineages in the thymus remain poorly understood. Although it has been relatively easy to direct differentiation of CD4 single positive (CD4+) cells using combinations of antibodies and pharmacological agents that mimic receptor engagements, equivalent stimuli do not induce efficient(More)
VGF is a protein expressed by neurons and processed into several peptides. It plays a role in energy homeostasis and promotes growth and survival. Recently, VGF mRNA was detected in peripheral leukocytes. Since it is known that aging is associated with a decrease in the development and function of neuronal as well as immune cells, we addressed the question(More)
We previously demonstrated that Akt differentially modulated a subset of NF-kB target genes during T cell activation. In the current study, we further explored the broader effects of Akt inhibition on T cell gene induction. Global microarray analysis was used to characterize T helper cell transcriptional responses following antigen receptor stimulation in(More)
A recent hypothesis suggests that a high glycaemic load diet-associated increase of insulin-like growth factor-1 (IGF-1) and insulin may promote acne by reducing nuclear localization of the forkhead box-O1 (FoxO1) transcription factor via activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. Using SZ95 sebocytes as a model, we investigated the(More)
Secretion of VGF is increased in cerebrospinal fluid and blood in neurodegenerative disorders like Alzheimer's disease (AD) and VGF is a potential biomarker for these disorders. We have shown that VGF is expressed in peripheral T cells and is correlated with T cell survival and cytokine secretion. The frequency of VGF+CD3+ T cells increases with normal(More)