Kidney injury molecule-1 staining in renal allograft biopsies 10 days after transplantation is inversely correlated with functioning proximal tubular epithelial cells.

Background: Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are promising biomarkers for monitoring delayed graft function (DGF) after kidney transplantation. Here we investigated localization and distribution of KIM-1 and NGAL staining in renal allograft biopsies and studied their association with histological features, functional DGF (fDGF) and the tubular function slope (TFS), a functioning proximal tubular epithelial cell (PTEC) marker.

Methods: Day 10 protocol biopsies of 64 donation after circulatory death recipients were stained for KIM-1 and NGAL and the positive area was quantified using ImageJ software.

Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members.

IL-35 is a cytokine of the IL-12 family, existing as a heterodimer of IL-12p35 and Ebi3. IL-35 has anti-inflammatory properties and is produced by regulatory T cells in humans and mice, where it is required for optimal suppression of immune responses. Distinct from other IL-12 cytokines, the expression of IL-35 has not been described in antigen-presenting cells.

Phagocytosis of apoptotic or necrotic cells differentially regulates the transcriptional expression of IL-12 family members in dendritic cells.

Uptake of apoptotic cells by DCs is considered to contribute to induction and maintenance of immunological tolerance. TolDCs are sought after as cellular therapy in transplantation and autoimmunity and can be generated in vitro using GCs. In this study, we investigated how uptake of dead cells affects the production and expression of different members of the IL-12 family by immature DCs or TolDCs.

Subsets of human type 2 macrophages show differential capacity to produce reactive oxygen species.

Reactive oxygen species (ROS) produced by macrophages have recently been shown to have immunosuppressive properties and induce regulatory T cells. Here we investigated the ROS producing capacity of well-defined human Mph2 subsets and studied the contribution of ROS in the Mph-T cell interaction. Mph were generated from monocytes using M-CSF (Mph2), IL-4 (Mph2a), or IL-10 (Mph2c).

Dexamethasone increases ROS production and T cell suppressive capacity by anti-inflammatory macrophages.

Macrophages have been demonstrated to suppress T cell responses by producing reactive oxygen species (ROS) leading to the subsequent induction of T regulatory cells in a ROS-dependent manner. Macrophages may therefore be instrumental in downregulating T cell responses in situations of exacerbated immune responses. Here we investigated the effect of immunosuppressive drugs on ROS production by macrophage subsets and the subsequent effects on T cell activation.

A nonredundant role for canonical NF-κB in human myeloid dendritic cell development and function.

The plastic role of dendritic cells (DCs) in the regulation of immune responses has made them interesting targets for immunotherapy, but also for pathogens or tumors to evade immunity. Functional alterations of DCs are often ascribed to manipulation of canonical NF-κB activity. However, though this pathway has been linked to murine myeloid DC biology, a detailed analysis of its importance in human myeloid DC differentiation, survival, maturation, and function is lacking.

Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species.

The phagocyte NAPDH-oxidase complex consists of several phagocyte oxidase (phox) proteins, generating reactive oxygen species (ROS) upon activation. ROS are involved in the defense against microorganisms and also in immune regulation. Defective ROS formation leads to chronic granulomatous disease (CGD) with increased incidence of autoimmunity and disturbed resolution of inflammation.

Renal tubular epithelial cells modulate T-cell responses via ICOS-L and B7-H1.

Background: Renal tubular epithelial cells (TECs) play an active role in renal inflammation. Previous studies have demonstrated the capacity of TECs to modulate T-cell responses both positively and negatively. Recently, new costimulatory molecules [inducible T cell costimulator-L (ICOS-L) and B7-H1] have been described, which appear to be involved in peripheral T-cell activation.

MIP-3alpha/CCL20 in renal transplantation and its possible involvement as dendritic cell chemoattractant in allograft rejection.

Graft-infiltrating dendritic cells (DC) and alloreactive T lymphocytes play a critical role in renal allograft rejection. Renal proximal tubular epithelial cells (TEC) are considered as active players in the attraction of leukocytes during renal inflammatory responses. Macrophage inflammatory protein (MIP)-3alpha/CCL20 is a major chemokine expressed by epithelial cells that attracts immature DC.

The novel cyclophilin-binding drug sanglifehrin A specifically affects antigen uptake receptor expression and endocytic capacity of human dendritic cells.

Sanglifehrin A (SFA) is a recently developed immunosuppressant that belongs to the family of immunophilin-binding ligands. SFA is a cyclophilin A-binding immunosuppressive drug with a novel, but unidentified, mechanism of action. Several reports exist about the effect of SFA on T cells, but its effect on the initiators of the immune response, i.

Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression.

The longevity of dendritic cells (DCs) is a critical regulatory factor influencing the outcome of immune responses. Recently, we demonstrated that the immunosuppressive drug rapamycin (Rapa) specifically induces apoptosis in DCs but not in other myeloid cell types. The present study unraveled the mechanism used by Rapa to induce apoptosis in human monocyte-derived DCs.