CD40 blockade hampers IgG class-switch while enhancing Granzyme B production by transitional B cells.

CD40-CD40L interaction is crucial for the interplay between B and T cells and determines B cell fate. Here, we investigated the effects of CD40-CD40L inhibition on B cell subsets and cytokine production using the non-depleting monoclonal anti-CD40 antibody CFZ534. CFZ534 had no impact on B cell viability but inhibited TLR9-agonistic (CpG-ODN) CD40L- as well as CD40L-mediated proliferation.

Mast cells infiltrates are common in eosinophilic esophagitis and still elevated in histological remission: A digital evaluation in children.

Objectives: Eosinophilic esophagitis (EoE) is a type 2 inflammatory chronic allergic disease with several additional immune cell subsets being involved. The aim of this study was to assess the identification and quantification of mast cells (MC) infiltrates using an objective and examiner independent analysis via digital image analysis of digitized histochemically stained biopsies.

Methods: Biopsies were taken from the esophagus of 24 children and adolescents diagnosed with EoE and stained for MC and eosinophilic granulocytes using anti-CD117 and Congo red, respectively.

Pharmacodynamic effect of mTOR inhibition-based immunosuppressive therapy on dendritic cell and natural killer cell subsets after renal transplantation.

Background: mTOR inhibitor therapy is solely monitored via pharmacokinetics after kidney transplantation, which may not accurately reflect the effectiveness of PI3K-Akt-mTOR pathway blockade, potentially leading to inadequate or excessive immunosuppression. The pharmacodynamic effect of mTOR inhibition on natural killer (NK) cells and dendritic cell (DC) subsets after renal transplantation has not been investigated so far.

Methods: Phosphoflow cytometry was employed in this cross-sectional study to evaluate the extent of mTOR inhibition in peripheral DC and NK cell subsets by assessing p70S6 kinase phosphorylation in kidney transplant recipients treated with mTOR inhibitors either in combination with calcineurin inhibitors (mTORi + CNI, n = 17) or mycophenolate sodium (mTORi + MPA, n = 9).

Adenosine-generating CD39 plasmablasts predispose to successful infliximab therapy in pediatric IBD.

B cells display several immunoregulatory mechanisms including the production of interleukin-10. Ectonucleotidases like CD39 and CD73 influence immune homeostasis by metabolizing eATP and generating immunosuppressive adenosine. The major objective was to examine the expression of those immunoregulatory molecules on B-cell subsets, and, more specifically, to determine their association with an infliximab (IFX) treatment in a pediatric inflammatory bowel disease (IBD) cohort.

Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation.

Background: The mammalian target of rapamycin inhibitor (mTORi) therapy after kidney transplantation is solely monitored pharmacokinetically, not necessarily reflecting PI3K-Akt-mTOR pathway blockade efficacy leading to potential under-or overimmunosuppression.

Methods: In this cross-sectional study, phosphoflow cytometry was used to determine the efficacy of mTOR inhibition in peripheral T- and B-lymphocyte subsets by assessing p70S6 kinase (p70S6K) phosphorylation in renal transplant recipients upon treatment with a combination of either mTORi and calcineurin inhibitors (n = 18), or mTORi with mycophenolic acid (n = 9). Nine dialysis patients with end-stage renal disease and 17 healthy age-matched volunteers served as controls.

TNF promotes DECTIN2 family C-type lectin receptor expression in human macrophages.

TNF blockade constitutes an effective therapy for inflammatory bowel disease, yet increases the risk for infection, including active tuberculosis. The DECTIN2 family C-type lectin receptors MINCLE, MCL, and DECTIN2 sense mycobacterial ligands and activate myeloid cells. In mice, upregulation of DECTIN2 family C-type lectin receptor after stimulation with Mycobacterium bovis Bacille Calmette-Guérin requires TNF.

A Modified Surgical Technique for Kidney Transplantation in Mice.

Kidney transplantation in mice is a complicated and challenging surgery procedure. There are very few publications demonstrating the key steps of this operation. Therefore, this article introduces the technique and points out the surgical caveats associated with this operation.

Mucosal Mast Cell Distribution in the Gastrointestinal Tract of Children: A Preliminary Study for Establishing Reference Values.

Objectives: The physiological number and distribution of mast cells (MCs) in the pediatric gastrointestinal (GI) tract is not well defined and reference values of normality are missing. To define a physiological and disease defining cut-off, a systematic histological exploration of MC distribution from the esophagus to the rectum in healthy as well as in patients with gastrointestinal food allergies (GFA) was performed.

Methods: Nine pediatric subjects that exhibited unremarkable histopathological evaluations or underwent endoscopy for surveillance reasons after a previous polypectomy of single colonic juvenile polyps served as reference cohort.

Blood Circuit Reconstruction in an Abdominal Mouse Heart Transplantation Model.

The surgical technique of heterotopic abdominal heart transplantation in mice is a standard model for research in transplantation immunology. Here, the established technique for a modified blood circuit reconstruction in a heterotopic abdominal heart transplantation model is presented. This method uses the intrathoracic inferior vena cava (IIVC) instead of the pulmonary artery of the donor heart for the anastomosis to the inferior vena cava of the recipient.

Distribution and Cytokine Profile of Peripheral B Cell Subsets Is Perturbed in Pediatric IBD and Partially Restored During a Successful IFX Therapy.

Background: The role of B cells in inflammatory bowel disease (IBD) is ambiguous, as B cells may have both pathogenic and protective functions in IBD. We studied B cell subsets before and after initiation of an anti-tumor necrosis factor alpha (anti-TNFα) therapy in pediatric IBD. The aim of the study was to examine the behavior of B cells in pediatric IBD patients undergoing an anti-TNFα therapy and, more specifically, to clarify their association with a successful or an unsuccessful infliximab (IFX) treatment.

Persistent changes within the intrinsic kidney-associated NPY system and tubular function by litter size reduction.

Background: Intrauterine growth restriction (IUGR) is associated with an increased risk of renal diseases in adulthood. However, while low-birth-weight-infants often undergo accelerated postnatal growth, the impact of postnatal environmental factors such as nutrition and early postnatal stressors on renal development and function remains unclear. In this context, Neuropeptide Y (NPY) may act as a critical factor.

Upregulation of leptin-receptor in placental cells by hypoxia.

Objective: Leptin and its receptor (Ob-R) are co-expressed in human placenta suggesting auto- and paracrine mechanisms of the hormone. So far it is unclear, how changes in the placental environment affect Ob-R expression. Hence, the main purpose of the study was to investigate leptin receptor expression and regulation under hypoxic conditions.

Altered leptin secretion in hyperinsulinemic mice under hypoxic conditions.

Objective: Hypoxia and insulin are known key players in the activation leptin transcription and translation in vivo and in vitro. These insulin- and hypoxia-dependent effects are leptin transcription are mediated via independent elements on the leptin-promotor, even more coincubation of the two stimuli in vitro results in a supraadditive effect on leptin transcription. The aim of this study was to examine whether hyperinsulinemia is able to interfere with the hypoxia-driven expression of leptin in adipose and extra-adipose tissue in vivo.

Hypoxia-induced leptin production in human trophoblasts does not protect from apoptosis.

Objective: The ob-gene product, leptin, is an important regulator of placental and fetal development during pregnancy. Leptin, being induced by hypoxia in the placenta, is a known pro-apoptotic molecule in adipose tissue but is also known to inhibit apoptosis in other tissues like neuroblastoma cells. Based on these findings, we investigated if leptin has a pro- or anti-apoptotic effect on a trophoblastic cell line (JAr cells) in the presence or absence of oxygen.

Differential regulation of leptin synthesis in rats during short-term hypoxia and short-term carbon monoxide inhalation.

Leptin is a circulating hormone that is secreted primarily by adipose tissue. However, recent studies have demonstrated leptin production by other tissues, including placenta, stomach, kidney, liver, and lung, a process not only activated by stimuli such as insulin or corticosteroids, but also by hypoxia, which is mediated by the hypoxia inducible factor-1. In contrast to this fact, smokers have lower plasma leptin levels.

Inducible expression of hypoxia-inducible factor 1alpha (HIF-1alpha) as a tool for studying HIF-1alpha-dependent gene regulation during normoxia in vitro.

The hypoxia-inducible factor 1alpha (HIF-1alpha), a member of the PAS superfamily, is a global regulator of cellular and systemic O(2) homeostasis as well as embryonic development. As the activity of HIF-1alpha is increased by a lowered oxygen tension in vivo and in vitro, we established a cell line producing high amounts of HIF-1alpha under normoxic conditions. As this overexpression was inducible by doxycycline, we can now provide a system to study HIF-1alpha-dependent gene regulation under normoxic as well as hypoxic conditions.