Natural killer cells modulate motor neuron-immune cell cross talk in models of Amyotrophic Lateral Sclerosis.

In amyotrophic lateral sclerosis (ALS), immune cells and glia contribute to motor neuron (MN) degeneration. We report the presence of NK cells in post-mortem ALS motor cortex and spinal cord tissues, and the expression of NKG2D ligands on MNs. Using a mouse model of familial-ALS, hSOD1, we demonstrate NK cell accumulation in the motor cortex and spinal cord, with an early CCL2-dependent peak.

IFN-γ/IL-6 and related cytokines in chronic spontaneous urticaria: evaluation of their pathogenetic role and changes during omalizumab therapy.

Background: Recent studies highlight that high levels of cytokines may precede the onset of many systemic autoimmune disorders and may also be related to chronic spontaneous urticaria (CSU) activity.

Methods: Eight patients with CSU candidate to omalizumab therapy were enrolled. Four healthy controls were included with the purpose of comparing baseline cytokine levels.

Gut microbiota alterations affect glioma growth and innate immune cells involved in tumor immunosurveillance in mice.

Glioma is a CNS tumor with few therapeutic options. Recently, host microbiota has been involved in the immune modulation of different tumors, but no data are available on the possible effects of the gut-immune axis on brain tumors. Here, we investigated the effect of gut microbiota alteration in a syngeneic (GL261) mouse model of glioma, treating mice with two antibiotics (ABX) and evaluating the effects on tumor growth, microbe composition, natural killer (NK) cells and microglia phenotype.

H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma.

Background: Glioma is the most common and primary brain tumors in adults. Despite the available multimodal therapies, glioma patients appear to have a poor prognosis. The Hedgehog (Hh) signaling is involved in tumorigenesis and emerged as a promising target for brain tumors.

Ca-activated K channels modulate microglia affecting motor neuron survival in hSOD1 mice.

Recent studies described a critical role for microglia in amyotrophic lateral sclerosis (ALS), where these CNS-resident immune cells participate in the establishment of an inflammatory microenvironment that contributes to motor neuron degeneration. Understanding the mechanisms leading to microglia activation in ALS could help to identify specific molecular pathways which could be targeted to reduce or delay motor neuron degeneration and muscle paralysis in patients. The intermediate-conductance calcium-activated potassium channel KCa3.

Human nasal immune system: a special site for immune response establishment.

The mucosal immune system located in correspondence to the olfactory organs in adult humans is not well identifiable but has proven important in establishing an effective immune response against inhaled antigens, including the generation of Helper 1 (TH1)- and TH2-cells, cytotoxic T lymphocytes (CTLs), plasma cells (PCs) and memory B cells. It is constituted by a diffused network of cells of epithelial and immune origin, as well as organized lymphoid tissue, where each component has a role in the initiation and maintenance of a long-lasting immune response, which is evoked not only in the oral and nasal cavities but also in the respiratory, intestinal and genito-urinary tracts. These peculiarities, in association to the easy anatomical accessibility of such immunological site, render the nasal mucosa a good candidate for the development of vaccine, even if a better understanding of the mechanism of the immune response induction as well as finding a safe adjuvant are necessary.

Environmental stimuli shape microglial plasticity in glioma.

In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, which contribute to tumor growth and to maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate that housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of infiltrating myeloid cells, by modulating inflammatory gene expression. Under these conditions, the branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted.

WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes.

Context: Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available.

Objectives: To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation.

Design And Participants: For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes.

Circulating IL-8 levels are increased in patients with type 2 diabetes and associated with worse inflammatory and cardiometabolic profile.

Aims: Interleukin-8 (IL-8) is a chemokine involved in systemic immunity, macrophages infiltration and activation in adipose tissue and may play a significant role in the pathogenesis of type 2 diabetes (T2D) and atherosclerosis. Aims of this study were to evaluate circulating IL-8 levels in adult patients with T2D in comparison with non-diabetic subjects and to describe clinical and biochemical correlates of IL-8 concentration.

Methods: For this cross-sectional study, we enrolled 79 consecutive T2D individuals referring to our diabetes outpatient clinics at Sapienza University of Rome, and 37 sex, age and BMI comparable non-diabetic subjects as a control group.

The Glycoside Oleandrin Reduces Glioma Growth with Direct and Indirect Effects on Tumor Cells.

Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na/K-ATPase. In addition to its known effects on cardiac muscle, recent and evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors.

Local allergic rhinitis in children: Novel diagnostic features and potential biomarkers.

Background: Local allergic rhinitis (LAR) is a phenotype of rhinitis that has been poorly studied in children. It is characterized by the same symptoms of allergic rhinitis but with the absence of markers of systemic atopy.

Objective: To identify children affected by LAR and to analyze the pathogenesis of this disease.

KCa3.1 channel inhibition sensitizes malignant gliomas to temozolomide treatment.

Malignant gliomas are among the most frequent and aggressive cerebral tumors, characterized by high proliferative and invasive indexes. Standard therapy for patients, after surgery and radiotherapy, consists of temozolomide (TMZ), a methylating agent that blocks tumor cell proliferation. Currently, there are no therapies aimed at reducing tumor cell invasion.

Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice.

Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth.

Increased IL-17, a Pathogenic Link between Hepatosplenic Schistosomiasis and Amyotrophic Lateral Sclerosis: A Hypothesis.

The immune system protects the organism from foreign invaders and foreign substances and is involved in physiological functions that range from tissue repair to neurocognition. However, an excessive or dysregulated immune response can cause immunopathology and disease. A 39-year-old man was affected by severe hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis.

Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death.

Upon noxious insults, cells of the brain parenchyma activate endogenous self-protective mechanisms to counteract brain damage. Interplay between microglia and astrocytes can be determinant to build a physiological response to noxious stimuli arisen from injury or stress, thus understanding the cross talk between microglia and astrocytes would be helpful to elucidate the role of glial cells in endogenous protective mechanisms and might contribute to the development of new strategy to mobilize such program and reduce brain cell death. Here we demonstrate that chemokines CX3CL1 and CXCL16 are molecular players that synergistically drive cross-talk between neurons, microglia and astrocytes to promote physiological neuroprotective mechanisms that counteract neuronal cell death due to ischemic and excitotoxic insults.

CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's syndrome.

Objectives: Primary SS is an autoimmune disease characterized by chronic lymphocytic inflammation and ectopic germinal centre (GC) formation within salivary glands. Fractalkine (CX3CL1), associated with the pathogenesis of RA, is the sole member of the CX3C chemokine (CK) family and acts as an adhesion and chemotactic molecule. The objectives of this work are to determine to what extent CX3CL1 and its receptor CX3CR1 expression might be altered in salivary glands obtained from patients and to establish whether these CKs might be involved in SS ectopic lymphoneogenesis.

Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential for migration.

Glioblastoma (GBM) is the most common and aggressive form of brain tumor, characterized by high migratory behavior and infiltration in brain parenchyma which render classic therapeutic approach ineffective. The migratory behaviour of GBM cells could be conditioned by a number of tissue- and glioma-derived cytokines and growth factors. Although the pro-migratory action of CXCL12 on GBM cells in vitro and in vivo is recognized, the molecular mechanisms involved are not clearly identified.

Modulatory Effect of Gliadin Peptide 10-mer on Epithelial Intestinal CACO-2 Cell Inflammatory Response.

Celiac Disease (CD) is a chronic inflammatory enteropathy, triggered in genetically susceptible individuals by dietary gluten. Gluten is able to elicit proliferation of specific T cells and secretion of inflammatory cytokines in the small intestine. In this study we investigated the possibility that p10-mer, a decapeptide from durum wheat (QQPQDAVQPF), which was previously shown to prevent the activation of celiac peripheral lymphocytes, may exert an inhibitory effect on peptic-tryptic digested gliadin (PT-Gly)-stimulated intestinal carcinoma CACO-2 cells.

Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease.

Mucosal interleukin (IL)-17A-producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ-producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL.

Attenuation of PI3K/Akt-mediated tumorigenic signals through PTEN activation by DNA vaccine-induced anti-ErbB2 antibodies.

By studying BALB/c mice deficient in immune components, we show that the protective immunity to rat ErbB2(+) tumors rests on the Ab response elicited by the electroporation of a DNA vaccine encoding the extracellular and transmembrane domains of rat ErbB2. In vivo, the adoptive transfer of vaccine-elicited anti-rat ErbB2 Abs protected against a challenge of rat ErbB2(+) carcinoma cells (TUBO cells). In vitro, such Abs inhibited TUBO cell growth by impairing cell cycle progression and inducing apoptosis.