Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands.

Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation.

Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison.

Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.

Methods And Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days.

Features and roles of T helper 22 cells in immunological diseases and malignancies.

T helper 22 (Th22) cell populations are a newly identified subset of CD4  T cells that primarily mediate biological effects on the epithelial barrier through interleukin (IL)-22. Although, new studies showed that both Th22 and IL-22 are closely associated with the pathogenesis of inflammatory, autoimmune and allergic disease as well as malignancies. In this review, we aim to describe the development and characteristics of Th22 cells as well as their roles in the immunopathogenesis of immune-related disorders and cancer.

The Potential Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Epilepsy Pathogenesis.

Within the pathophysiology of epilepsy, as a chronic brain disorder, the involvement of neuroinflammation has been extensively implied. Recurrent seizures of epilepsy have been associated with elevated levels of immune mediators that seem to play a pivotal role in triggering them. Neurons, glia, and endothelial cells of the blood-brain barrier (BBB) take part in such inflammatory processes by expressing receptors of associated mediators through autocrine and paracrine stimulation of intracellular signaling pathways.

Anti-Inflammatory Effect of KW-2449 on Autoimmune Encephalomyelitis: An Experimental Study on Mice.

Background: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells, but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet.

The Effects of G2013 (α-L-guluronic Acid) in a Pentylenetetrazole-induced Kindling Animal Model of Epilepsy.

Recent studies have reported observing antioxidant, anti-inflammatory, and anti-aging properties of α-L-Guluronic acid (G2013) in animal and human studies. It has been theorized that the antioxidant and anti-inflammatory properties of G2013 might be beneficial in epilepsy treatment. We sought to determine G2013's effects on epileptic activity in a kindling-induced animal model.

Interleukin-1β and interleukin-6 in Common Variable Immunodeficiency and their association with subtypes of B cells and response to the Pneumovax-23 vaccine.

Introduction: Common Variable Immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiencies. Current research data show altered B cells, TLRs, and cytokine profile in CVID patients. The aim of this study was to determine levels of IL-1β and IL-6 in CVID patients in response to TLRs stimulation and the association of these cytokines with subtypes of B cells and response to Pneumovax-23 vaccination.

The effects of cadmium exposure in the induction of inflammation.

Inflammation is a physiological process essential for maintaining homeostatic mechanisms in human, but however, exaggerated inflammatory responses are closely related to many chronic diseases. Cadmium (Cd) is a heavy metal with high toxicity when present in food, water and air has the potential of eliciting inflammatory reactions, with a major health risk to human. This review aimed to elucidate on the major routes of Cd exposure, the main organs affected by the exposure, the degree of toxicity as well as the roles of the toxic effects on the immune system which results to inflammatory responses.

Clinical, Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review.

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia, and recurrent infections.

Objective: Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency.

A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders.

The T helper 17 (Th17) cells contain a dynamic subset of CD4+ T-cells that are able to develop into other different lineage subsets, including the Th1-like Th17 cells. These cells co-express retinoic acid-related orphan receptor gamma t (RORγt) and transcription factor T-box-expressed-in-T-cells (T-bet) and produce both interleukin (IL)-17 and interferon (IFN)-γ. Recent reports have shown that Th1-like Th17 cells play crucial roles in the pathogenesis of autoimmune diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, as well as, some primary immunodeficiency with autoimmune features.

Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection.

The co-endemicity of malnutrition, erythrocytopathies, transmissible diseases and iron-deficiency contribute to the prevalence of chronic anaemia in many populations of the developing world. Although iron dietary supplementation is applied or recommended in at risk populations, its use is controversial due to undesirable outcomes, particularly regarding the response to infections, including highly prevalent malaria. We hypothesized that a boosted oxidative stress due to iron supplementation have a similar impact on malaria to that of hereditary anaemias, enhancing innate response and conditioning tissues to prevent damage during infection.

Experimental Immunization Based on Plasmodium Antigens Isolated by Antibody Affinity.

Vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. We used the sera of malaria self-resistant ICR mice to lethal Plasmodium yoelii yoelii 17XL for purification of their IgGs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to immunize BALB/c mice.

Differential immune response associated to malaria outcome is detectable in peripheral blood following Plasmodium yoelii infection in mice.

Malaria infection in humans elicits a wide range of immune responses that can be detected in peripheral blood, but we lack detailed long-term follow-up data on the primary and subsequent infections that lead to naturally acquired immunity. Studies on antimalarial immune responses in mice have been based on models yielding homogenous infection profiles. Here, we present a mouse model in which a heterogeneous course of Plasmodium yoelii lethal malaria infection is produced in a non-congenic ICR strain to allow comparison among different immunological and clinical outcomes.

Differential carbonylation of cytoskeletal proteins in blood group O erythrocytes: potential role in protection against severe malaria.

The molecular basis for the prevalence of blood group O in regions where malaria is endemic remains unclear. In some genetic backgrounds oxidative modifications have been linked to a reduced susceptibility to severe malaria disease. Through redox proteomics, we detected differences in carbonylated membrane proteins among the different blood groups, both in Plasmodium-infected and uninfected erythrocytes (RBC).

Plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified IgG antibodies from malaria-resistant mice.

As the search for an effective human malaria vaccine continues, understanding immune responses to Plasmodium in rodent models is perhaps the key to unlocking new vaccine strategies. The recruitment of parasite-specific antibodies is an important component of natural immunity against infection in blood-stage malaria. Here, we describe the use of sera from naturally surviving ICR mice after infection with lethal doses of Plasmodium yoelii yoelii 17XL to identify highly immunogenic blood-stage antigens.