Dichotomous role of TGF-β controls inducible regulatory T-cell fate in allergic airway disease through Smad3 and TGF-β-activated kinase 1.

Background: Inducible CD4CD25 regulatory T (iTreg) cells can become pathogenic effector cells, enhancing lung allergic responses.

Objective: We aimed to define the underlying cellular and molecular pathways activated by TGF-β, which determine the suppressor or enhancing activities of iTreg cells.

Methods: Sensitized wild-type and CD8-deficient (CD8) mice were challenged with allergen.

Hypoxia enhances CD8 T2 cell-dependent airway hyperresponsiveness and inflammation through hypoxia-inducible factor 1α.

Background: CD8 type 2 cytotoxic T (T2) cells undergo transcriptional reprogramming to IL-13 production in the presence of IL-4 to become potent, steroid-insensitive, pathogenic effector cells in asthmatic patients and in mice in a model of experimental asthma. However, no studies have described the effects of hypoxia exposure on T2 cell differentiation.

Objective: We determined the effects of hypoxia exposure on IL-13-producing CD8 T2 cells.

Activation of p70S6 Kinase-1 in Mesenchymal Stem Cells Is Essential to Lung Tissue Repair.

All-trans retinoic acid (ATRA) or mesenchymal stem cells (MSCs) have been shown to promote lung tissue regeneration in animal models of emphysema. However, the reparative effects of the combination of the two and the role of p70S6 kinase-1 (p70S6k1) activation in the repair process have not been defined. Twenty-one days after intratracheal instillation of porcine pancreatic elastase (PPE), MSC and/or 10 days of ATRA treatment was initiated.

Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7.

We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily.

Mesenchymal Stem Cells Recruit CCR2 Monocytes To Suppress Allergic Airway Inflammation.

Mesenchymal stem cells (MSC) exert immune modulatory properties and previous studies demonstrated suppressive effects of MSC treatment in animal models of allergic airway inflammation. However, the underlying mechanisms have not been fully elucidated. We studied the role of MSC in immune activation and subsequent recruitment of monocytes in suppressing airway hyperresponsiveness and airway inflammation using a mouse model of allergic airway inflammation.

Dual-frequency ultrasonic treatment on microstructure and mechanical properties of ZK60 magnesium alloy.

Compared with other dual-frequency acoustic applications, melt-treatment with dual-frequency ultrasound was less researched, especially in magnesium field. In this present work, traditional single-frequency ultrasonic field (SUF) treatment and dual-frequency ultrasonic field (DUF) treatment were used to refine the as-cast microstructure and improve the mechanical properties of the ZK60 (Mg-Zn-Zr) magnesium alloy. The influences of DUF on the microstructure evolution and mechanical properties were systematically investigated, and the cavitation bubble's dynamic behaviors were investigated by numerical simulation.

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7.

Two of the unsolved, important questions about epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-containing proteins, JMJD5 and JMJD7, have divalent cation-dependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 and JMJD7, acting as aminopeptidases, progressively digest the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones.

1,25D3 prevents CD8(+)Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter.

Effector CD8(+) T cells convert from IFN-γ(+) (Tc1) to IL-13(+) (Tc2) cells in the presence of IL-4. Underlying regulatory mechanisms are not fully defined. Here, we show that addition of 1,25D3, the active form of vitamin D3, during CD8(+) T-cell differentiation prevents IL-4-induced conversion to IL-13-producers.

The structural basis of urea-induced protein unfolding in β-catenin.

Although urea and guanidine hydrochloride are commonly used to denature proteins, the molecular underpinnings of this process have remained unclear for a century. To address this question, crystal structures of β-catenin were determined at various urea concentrations. These structures contained at least 105 unique positions that were occupied by urea molecules, each of which interacted with the protein primarily via hydrogen bonds.

Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands.

The short palate, lung and nasal epithelial clone 1 (SPLUNC1) protein is a member of the palate, lung, and nasal epithelium clone (PLUNC) family, also known as bactericidal/permeability-increasing (BPI) fold-containing protein, family A, member 1 (BPIFA1). SPLUNC1 is an abundant protein in human airways, but its function remains poorly understood. The lipid ligands of SPLUNC1 as well as other PLUNC family members are largely unknown, although some reports provide evidence that lipopolysaccharide (LPS) could be a lipid ligand.

Structural insights into cofactor recognition of yeast mitochondria 3-oxoacyl-ACP reductase OAR1.

3-Oxoacyl-(acyl-carrier-protein) reductase (OAR1 or FabG, EC.1.1.