Composition of the Cytochrome Complex with Cardiolipin by Thermal Lens Spectrometry.

Thermal lens spectrometry along with spectrophotometric titration were used to assess the composition of the complex of oxidized cytochrome (ferricytochrome ) with 1,1',2,2'-tetraoleyl cardiolipin, which plays a key role in the initiation of apoptosis. Spectrophotometric titration was carried out for micromolar concentrations at which the complex is mainly insoluble, to assess the residual concentration in the solution and to estimate the solubility of the complex. Thermal lens spectrometry was used as a method of molecular absorption spectroscopy, which has two advantages over conventional optical transmission spectroscopy: the higher sensitivity of absorbance measurements and the possibility of studying the light absorption by chromophores and heat transfer in complex systems, such as living cells or tissues.

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction. However, the molecular mechanisms that underlie this dysfunction remain unclear.

IL22 Promotes -Mutant Lung Cancer by Induction of a Protumor Immune Response and Protection of Stemness Properties.

Somatic mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a -induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-κB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4 T-helper cell response. IL22 is an effector molecule secreted by CD4 and γδ T cells that we previously found to be expressed in CC-LR mice.

Absence of Grail promotes CD8 T cell anti-tumour activity.

T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8 T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8 T cells is sufficient to repress established tumours.

Insights into the development and regulation of T follicular helper cells.

T follicular helper (Tfh) cells are specialized subset of T helper (Th) cells necessary for germinal center reaction, affinity maturation and the differentiation of germinal center B cells to antibody-producing plasma B cells and memory B cells. The differentiation of Tfh cells is a multistage, multifactorial process involving a variety of cytokines, surface molecules and transcription factors. While Tfh cells are critical components of protective immune responses against pathogens, regulation of these cells is crucial to prevent autoimmunity and airway inflammation.

Batf is important for IL-4 expression in T follicular helper cells.

Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus.

Grail controls Th2 cell development by targeting STAT6 for degradation.

T helper (Th)-2 cells are the major players in allergic asthma; however, the mechanisms that control Th2-mediated inflammation are poorly understood. Here we find that enhanced expression of Grail, an E3 ubiquitin ligase, in Th2 cells depends on interleukin (IL)-4-signalling components, signal transducer and activator of transcription 6 (Stat6) and Gata3, that bind to and transactivate the Grail promoter. Grail deficiency in T cells leads to increased expression of Th2 effector cytokines in vitro and in vivo and Grail-deficient mice are more susceptible to allergic asthma.

Reduced graft-versus-host disease in C3-deficient mice is associated with decreased donor Th1/Th17 differentiation.

Graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation is mediated by the activation of recipient dendritic cells and subsequent proliferation of donor T cells. The complement system was recently shown to modulate adaptive immunity through an interaction of the complement system and lymphocytes. Complement proteins participate in the activation of dendritic cells, antigen presentation to T cells, and proliferation of T cells.

STAT5 protein negatively regulates T follicular helper (Tfh) cell generation and function.

Recent work has identified a new subset of CD4(+) T cells named as Tfh cells that are localized in germinal centers and critical in germinal center formation. Tfh cell differentiation is regulated by IL-6 and IL-21, possibly via STAT3 factor, and B cell lymphoma 6 (Bcl6) is specifically expressed in Tfh cells and required for their lineage specification. In the current study, we characterized the role of STAT5 in Tfh cell development.

Autosomal recessive retinitis pigmentosa and E150K mutation in the opsin gene.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary disorders of the retina caused by mutation in genes of the photoreceptor proteins with an autosomal dominant (adRP), autosomal recessive (arRP), or X-linked pattern of inheritance. Although there are over 100 identified mutations in the opsin gene associated with RP, only a few of them are inherited with the arRP pattern. E150K is the first reported missense mutation associated with arRP.

Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo.

The retinoid cycle is a recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. Photoreceptor-specific retinol dehydrogenase (prRDH) catalyzes reduction of all-trans-retinal to all-trans-retinol and is thought to be a key enzyme in the retinoid cycle. We disrupted mouse prRDH (human gene symbol RDH8) gene expression by targeted recombination and generated a homozygous prRDH knock-out (prRDH-/-) mouse.

RANK, RANKL, OPG, and M-CSF expression in stromal cells during corneal wound healing.

Purpose: To examine the influx of monocytes into the cornea after epithelial scrape injury and the expression of chemokines that potentially regulate monocyte phenotype in cultured corneal fibroblasts and keratocytes in situ.

Methods: Monocytes were detected by immunocytochemistry for the monocyte-specific antigen CD11b, in unwounded and epithelial scrape-wounded mouse corneas. The receptor activator of NF-kappa B ligand (RANKL), osteoprotegerin (OPG), and monocyte chemotactic and stimulating factor (M-CSF) mRNAs were detected in cultured mouse stromal fibroblasts by RT-PCR and RNase protection assay.

Photoreceptor guanylate cyclase variants: cGMP production under control.

Changes in the Ca2+ concentration are thought to affect many processes, including signal transduction in a vast number of biological systems. However, only in few cases the molecular mechanisms by which Ca2+ mediates its action are as well understood as in phototransduction. In dark-adapted photoreceptor cells, the equilibrium level of cGMP is maintained by two opposing activities, such as phosphodiesterase (PDE) and guanylate cyclase (GC).

Soluble fusion proteins between single transmembrane photoreceptor guanylyl cyclases and their activators.

Among single-spanning transmembrane receptors (sTMRs), two guanylyl cyclase receptors, GC1 and GC2, are critically important during phototransduction in vertebrate retinal photoreceptor cells. Ca(2+)-free forms of guanylyl cyclase-activating proteins (GCAPs) stimulate GCs intracellularly by a molecular mechanism that is not fully understood. To gain further insight into the mechanism of activation and specificity among these proteins, for the first time, several soluble and active truncated GCs and fusion proteins between intracellular domains of GCs and full-length GCAPs were generated.