Atopy as an independent predictor for long-term patient and graft survival after kidney transplantation.

Background: Atopy is a genetic condition predisposing individuals to develop immunoglobulin E (IgE) against common allergens through T-helper 2 (Th2) polarization mechanisms. The impact of atopy on graft survival in solid organ transplantation is unknown.

Methodology: We analyzed 268 renal allograft recipients from the Swiss Transplant Cohort Study, a prospective multicenter cohort studying patients after solid organ transplantation, with a 9-year median follow-up (IQR 3.

Therapeutic Potential of Targeting Malt1-Dependent TCR Downstream Signaling to Promote the Survival of MHC-Mismatched Allografts.

Strategies targeting T cells are the cornerstone of immunosuppression after solid organ transplantation. The transcription factor NF-κB is a key regulator of downstream T-cell activation and induction of inflammatory mediators; its full activation via antigen receptor engagement requires both the scaffold and the protease activity of the paracaspase Malt1. Experimental studies have highlighted that Malt1-deficient mice were resistant to experimental autoimmune encephalomyelitis, although they lacked peripheral regulatory T cells (Treg).

Differential Effects of the Mitochondria-Active Tetrapeptide SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH) and Its Peptidase-Targeted Prodrugs in Experimental Acute Kidney Injury.

The mitochondria-active tetrapeptide SS-31 can control oxidative tissue damage in kidney diseases. To investigate other potential beneficial nephroprotective effects of SS-31, murine models of acute tubular injury and glomerular damage were developed. Reduction of acute kidney injury was demonstrated in mice treated with SS-31.

Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction.

Fibrosis is an inadequate response to tissue stress with very few therapeutic options to prevent its progression to organ dysfunction. There is an urgent need to identify drugs with a therapeutic potential for fibrosis, either by designing and developing new compounds or by repurposing drugs already in clinical use which were developed for other indications. In this Perspective, we summarize some pathways and biological targets involved in fibrosis development and maintenance, focusing on common mechanisms between organs and diseases.

Targeted γ-secretase inhibition of Notch signaling activation in acute renal injury.

The Notch pathway has been reported to control tissue damage in acute kidney diseases. To investigate potential beneficial nephroprotective effects of targeting Notch, we developed chemically functionalized γ-secretase inhibitors (GSIs) targeting γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransferase (γ-GCT), two enzymes overexpressed in the injured kidney, and evaluated them in in vivo murine models of acute tubular and glomerular damage. Exposure of the animals to disease-inducing drugs together with the functionalized GSIs improved proteinuria and, to some extent, kidney dysfunction.

SIgA-Shigella Immune Complexes Interact with Dectin-1 and SIGNR3 to Differentially Regulate Mouse Peyer's Patch and Mesenteric Lymph Node Dendritic Cell's Responsiveness.

In addition to contributing to immune exclusion at mucosal surfaces, secretory IgA (SIgA) made of polymeric IgA and secretory component is able to selectively reenter via microfold cells into Peyer's patches (PPs) present along the intestine and to associate with dendritic cells (DCs) of the CD11cCD11bMHCIIF4/80CD8phenotype in the subepithelial dome region and the draining mesenteric lymph nodes (MLNs). However, the nature of the receptor(s) for SIgA on murine PP and MLN DCs is unknown. We find that glycosylated secretory component moiety and polymeric IgA are both involved in the specific interaction with these cells.

Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β.

The importance of secretory IgA in controlling the microbiota is well known, yet how the antibody affects the perception of the commensals by the local immune system is still poorly defined. We have previously shown that the transport of secretory IgA in complex with bacteria across intestinal microfold cells results in an association with dendritic cells in Peyer's patches. However, the consequences of such an interaction on dendritic cell conditioning have not been elucidated.

Comparative genome analysis of Pseudomonas knackmussii B13, the first bacterium known to degrade chloroaromatic compounds.

Pseudomonas knackmussii B13 was the first strain to be isolated in 1974 that could degrade chlorinated aromatic hydrocarbons. This discovery was the prologue for subsequent characterization of numerous bacterial metabolic pathways, for genetic and biochemical studies, and which spurred ideas for pollutant bioremediation. In this study, we determined the complete genome sequence of B13 using next generation sequencing technologies and optical mapping.