Cytomegalovirus infection is associated with thymic dysfunction and chronic graft-versus-host disease after pediatric hematopoietic stem cell transplantation.

Pediatric hematopoietic stem cell transplantation (HSCT) is challenged by chronic graft-versus-host disease (cGvHD) significantly affecting survival and long-term morbidity, but underlying mechanisms including the impact of post-HSCT CMV infection are sparsely studied. We first investigated the impact of CMV infection for development of cGvHD in 322 children undergoing standard myeloablative HSCT between 2000 and 2018. Clinically significant CMV infection (n = 61) was an independent risk factor for chronic GvHD in a multivariable Cox regression analysis (HR = 2.

Thymic stromal lymphopoietin levels after allogeneic hematopoietic stem cell transplantation.

Background: Thymic stromal lymphopoietin (TSLP) is an immunoregulatory, Th2-polarizing cytokine produced by epithelial cells. We hypothesized that TSLP affects immune reconstitution after hematopoietic stem cell transplantation (HSCT) leading to increased alloreactivity.

Methods: We measured plasma TSLP by ELISA in 38 patients and assessed the immune reconstitution by flow cytometry.

Cladribine inhibits secretion of pro-inflammatory cytokines and phagocytosis in human monocyte-derived M1 macrophages in-vitro.

Cladribine (Cd) is a purine nucleoside analogue which in an oral formulation is approved for treatment of patients with multiple sclerosis (MS). It is known to mediate the effect through a short-term selective reduction of lymphocytes with minimal effect on the innate immune system. However, a few studies have emerged, that also demonstrate a beneficial immunomodulatory effect of cladribine on monocyte-derived cells.

Cryopreservation of peripheral blood mononuclear cells for use in proliferation assays: First step towards potency assays.

Investigational cell-based therapeutics are rapidly heading towards pivotal clinical trials. The premise is that the scientific rationale is well defined, and that product quality reflects exactly this. In vitro potency assays are necessary tools for evaluating cell products, and with potency assays comes high demands for standardization and reproducibility of the methods involved.

Multistrain Probiotic Increases the Gut Microbiota Diversity in Obese Pregnant Women: Results from a Randomized, Double-Blind Placebo-Controlled Study.

Background: Maternal obesity is associated with adverse pregnancy outcomes. Probiotic supplementation during pregnancy may have positive effects on blood glucose, gestational weight gain (GWG), and the risk of gestational diabetes mellitus [GDM and glycated hemoglobin (HbA1c)].

Objectives: This feasibility study involved a daily probiotic intervention in obese pregnant women from the early second trimester until delivery.

Development of an Assay to Assess Pharmacological Compounds and Reversion of Tumor-Derived Immunosuppression of Dendritic Cells.

Background: Cancer immunotherapies have achieved much success and have become the forefront treatment of cancers previously associated with poor prognosis. However, a major challenge in cancer immunotherapies remains the heterogeneity of the immunoregulatory capacities of cancers, and not all patients of a given cancer responds to current therapeutic strategies. To address this issue and to facilitate the development of new pharmacological compounds, we here describe an model of dendritic cell suppression by cancer cells.

TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice.

Background/objectives: TL1A is a pro-inflammatory cytokine that is homologous to TNFα and connected with the development of several chronic inflammatory disorders. The preliminary results of this study indicated reduced fat accumulation in 9-month-old TL1A-deficient mice at steady state. Thus, the objective was to investigate whether TL1A-deficient mice are resistant to the development of high-fat (HF) diet-induced obesity and to investigate the impact on lymphocyte infiltration in adipose tissue.

Upregulation of PD-1 follows tumour development in the AOM/DSS model of inflammation-induced colorectal cancer in mice.

Chronic inflammation may drive development of cancer as observed in inflammation-induced colorectal cancer (CRC). Though immune cells can infiltrate the tumour microenvironment, cancer cells seem to evade anti-tumour responses, which is one of the established hallmarks of cancer. Targeting the programmed cell death protein-1 (PD-1)/PD-L1 signalling pathway is currently at the forefront in the development of anti-tumour immunity-based therapies for multiple malignancies.

TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice.

Background: The tumor necrosis factor alpha (TNFα)-homologous cytokine TL1A is emerging as a major player in intestinal inflammation. From in vitro experiments on human lymphocytes, TNF-like molecule 1A (TL1A) is known to activate a highly inflammatory lymphoid response in synergy with interleukin (IL)-12 and IL-18. Carriers of specific genetic polymorphisms associated with IL-12, IL-18, or TL1A signaling have increased Crohn's disease risk, and all 3 cytokines are upregulated during active disease.

Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis.

Background And Aims: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.

Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein.

Nanocarriers based on inverse hexagonal liquid crystalline phases (hexosomes) show promising potential as vaccine delivery systems. Their unique internal structure, composed of both lipophilic domains and water-containing channels, renders them capable of accommodating immunopotentiating compounds and antigens. However, their adjuvant properties are poorly understood.

Donor Genotype in the Interleukin-7 Receptor α-Chain Predicts Risk of Graft-versus-Host Disease and Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation.

The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for T cell generation in thymus and peripheral T cell homeostasis. In this study, we investigated the impact of the single nucleotide polymorphism in the IL-7 receptor α-chain (IL-7Rα) which has previously been associated with several autoimmune diseases.

Brief Report: CD52 Expression on CD4+ T Cells in HIV-Positive Individuals on cART.

Background: HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART).

Reconstitution of Th17, Tc17 and Treg cells after paediatric haematopoietic stem cell transplantation: Impact of interleukin-7.

Successful reconstitution of T lymphocytes after allogeneic haematopoietic stem cell transplantation (HSCT) is needed to establish the graft-versus-leukaemia effect and an effective anti-microbial defense, but the ratio between functionally different T-cell subsets needs to be balanced to avoid graft-versus-host disease (GVHD). IL-7 is essential for T-cell generation in the thymus and peripheral T-cell homeostasis. High IL-7 levels have been associated with impaired T-cell reconstitution, increased risk of acute GVHD and treatment-related mortality, but the underlying cellular mechanisms behind these associations have not been investigated previously.

Expression and Localization of miR-21 and miR-126 in Mucosal Tissue from Patients with Inflammatory Bowel Disease.

Background: microRNAs (miRNAs) are small noncoding RNAs that guide degradation of mRNA and regulate protein expression. miRNA based diagnostic biomarkers for ulcerative colitis (UC) and Crohn's disease (CD) are emerging but information about the cellular localization of many miRNAs is limited and more detailed histologic evaluation of miRNA expression patterns is needed to understand their immunobiological function.

Methods: Formalin-fixed paraffin-embedded colon biopsies from 10 patients with UC and 8 patients with CD together with 9 controls were examined by RT-qPCR and quantitative in situ hybridization (ISH).

Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn: study protocol for a randomized controlled trial.

Background: Maternal obesity is associated with increased risks of adverse pregnancy-related complications and outcomes for both mothers and infants. Overweight and obese women have an increased risk of pregnancy-induced hypertension, preeclampsia and gestational diabetes mellitus (GDM). Infant Body Mass index (BMI) and the risk of obesity in adulthood are related to maternal gestational weight gain (GWG).

Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice.

Background: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation.

Methods: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice.

Age and gender leucocytes variances and references values generated using the standardized ONE-Study protocol.

Flow cytometry is now accepted as an ideal technology to reveal changes in immune cell composition and function. However, it is also an error-prone and variable technology, which makes it difficult to reproduce findings across laboratories. We have recently developed a strategy to standardize whole blood flow cytometry.

An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression.

Previous studies have shown promising results when using an agonistic anti-4-1BB antibody treatment against established tumors. While this is promising, this type of treatment can induce severe side effects. Therefore, we decided to incorporate the membrane form of 4-1BB ligand (4-1BBL) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA).

Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture.

Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations.