Altered signaling through IL-12 receptor in children with very high serum IgE levels

An alteration of Th1/Th2 homeostasis may lead to diseases in humans. In this study, we investigated whether an impaired IL-12R signaling occurred in children with elevated serum IgE levels divided on the basis of the IgE levels (group A: >2000 kU/l; group B: <2000 kU/l). We evaluated the integrity of the IL-12R signaling through the analysis of phosphorylation/activation of STAT4, and mRNA expression and membrane assembly of the receptor chains. At a functional level, a proliferative defect of lymphocytes from group A patients was observed. In these patients, an abnormal IL-12R signaling was documented, and this finding was associated with abnormal expression of the IL-12Rb2 chain. Our data indicate that in patients with very high IgE levels the generation of Th1 response is impaired, and that this abnormality associates with abnormal IL-12R signaling

From Murine to Human Nude/SCID: The Thymus, T-Cell Development and the Missing Link

Primary immunodeficiencies (PIDs) are disorders of the immune system, which lead to increased susceptibility to infections. T-cell defects, which may affect T-cell development/function, are approximately 11% of reported PIDs. The pathogenic mechanisms are related to molecular alterations not only of genes selectively expressed in hematopoietic cells but also of the stromal component of the thymus that represents the primary lymphoid organ for T-cell differentiation. With this regard, the prototype of athymic disorders due to abnormal stroma is the Nude/SCID syndrome, first described in mice in 1966. In man, the DiGeorge Syndrome (DGS) has long been considered the human prototype of a severe T-cell differentiation defect. More recently, the human equivalent of the murine Nude/SCID has been described, contributing to unravel important issues of the T-cell ontogeny in humans. Both mice and human diseases are due to alterations of the FOXN1, a developmentally regulated transcription factor selectively expressed in skin and thymic epithelia

Resilience in Computer System and Network

La resilienza informatica è la capacità di un sistema di continuare a garantire dei servizi, malgrado agenti contrari, via via più difficili da trattare, quali ad es.: usura, cambiamenti del software, guasti, attacchi alla sicurezza. La capacità di resistenza e recupero dei vari sistemi, indotta e preparata dall’ essere umano, ci ha permesso di venire a conoscenza di informazioni e dati (sociali) nascosti, che hanno aumentato il nostro sapere

A comprehensive database of Algal biological data.

There is significant interest worldwide on ‘algal products’, with news about investments and research programmes, emerging on an almost daily basis. In recent years, microalgae have garnered interest for producing valuable molecules with high commercial importance in the food industry and aquaculture as a natural source of high-value products such as carotenoids, polysaccharides, fatty acids, steroids and algal toxins, ranging from therapeutic proteins to biofuels. The ability of microalgae to survive or proliferate over a wide range of environmental conditions is, to a large extent, reflected in the tremendous biodiversity. The research put some effort to increase the knowledge in algal systems, for their capacity to fine tuning metabolism efficiently in response to changes in environmental conditions. Along with this effort there is an imperative need to integrate large scale data sets from high throughput experimental techniques using computational methods and database resources to provide comprehensive information about the molecular data. Only few databases are present so far, however, no single database exists that provides the necessary information on algal's metabolite already characterised. To accelerate the development of algal product production, we have developed a custom-design database, Microalgae Database (MIDA). That could become an important tool in assisting scientists. The data are being collected from scientific experiments, published literature, high throughput experiment technology and computational analyses. The customized search engine and the data structure of this database will enable to extract exhaustive informations, joining different kinds of data, and develop various statistics

Gamma chain transducing element: a shared pathway between endocrine and immune system

Several molecules, involved in the intracellular communication network, have been identified as the cause of primary immunodeficiencies. In most cases, these molecules are exclusively expressed in hematopoietic cells, being involved in cell development and/or functionality of terminal differentiated cells of immune system. In the case of gamma c, the abundance of the protein suggests a potential pleiotropic effect of the molecule. Immune and endocrine systems participate to an integrated network of soluble mediators that communicate and coordinate responsive cells to achieve effector functions in an appropriate fashion. It has been demonstrated a novel dependence of GH signaling on the common cytokines receptor gamma c in certain cell types, supporting the hypothesis of an interplay between endocrine and immune system. The evidence that different receptors share a few molecules may certainly lead to a better knowledge on the mechanism of coordination and integration of several pathways implicated in the control of cell growth and proliferation under physiological or pathogenic conditions. This review focuses on the gamma c as a common transducing element shared between several cytokines and growth hormone receptors, indicating a further functional link between endocrine and immune system

The cellular amount of the common γ-chain influences spontaneous or induced cell proliferation

Mutations of the IL2RG encoding the common γ-chain (γc) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that γc could have a role per se in malignant lymphoproliferation. The γc is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lympho-blastoid cell lines lacking γc, we demonstrate that self-sufficient growth was strongly dependent on γc expression. Furthermore, a correlation between γc amount and the extent of constitutive activation of JAK3 was found. The reduction of γc protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that γc plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation. Copyright © 2009 by The American Association of Immunologists, Inc

Role of the common γ chain in cell cycle progression of human malignant cell lines

The γ-chain (γc) is a transducing element shared between several cytokine receptors whose alteration causes X-linked severe combined immunodeficiency. Recently, a direct involvement of γc in self-sufficient growth in a concentration-dependent manner was described, implying a direct relationship between the amount of the molecule and its role in cell cycle progression. In this study, we evaluate whether γc expression could interfere in cell cycle progression also in malignant hematopoietic cells. Here, we first report that in the absence of γc expression, lymphoblastoid B-cell lines (BCLs) die at a higher extent than control cells. This phenomenon is caspase-3 independent and is associated to a decreased expression of the antiapoptotic Bcl-2 family members. By contrast, increased expression of γc protein directly correlates with spontaneous cell growth in several malignant hematopoietic cell lines. We, also, find that the knockdown of γc protein through short interfering RNA is able to decrease the cell proliferation rate in these malignancies. Furthermore, an increased expression of all D-type cyclins is found in proliferating neoplastic cells. In addition, a direct correlation between the amount of γc and cyclins A2 and B1 expression is found. Hence, our data demonstrate that the amount of the γc is able to influence the transcription of genes involved in cell cycle progression, thus being directly involved in the regulatory control of cell proliferation of malignant hematopoietic cells