Jan 17, 2019 Last Updated 12:56 PM, Jan 17, 2019
AINI - Alessandro Leuti
Alessandro Leuti

Alessandro Leuti

Il 22 febbraio 2019, l'Aula Magna Giorgio De Sandre del Policlinico Universitario G.B. Rossi, a Verona, ospiterà l'incontro "Antibody-associated CNS disorders and theri differential diagnosis", patrocinato da AINI.

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T regulatory cells (Treg) have been reported to exert IL10-dependent beneficial effects during the aftermath of brain infarction, although their physiological role in this pathology has not been yet fully understood, mostly due to the fact that Treg cells are present only in low numbers around stroke area during the acute phase of the ischaemic episode (i.e. around one week later). According to this brief comunication, published on Nature last december, however, looking at a different time window might shed some light on the immunomodulatory role played by Tregs on ischaemic stroke.

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Mandatory vaccination in Italy - a reaction mostly driven by the drop of immunization coverage threshold below 95% - has unleashed significant uproar in some political and social environment due to a spreading fear for adverse reactions, mostly fed by misinformation and populism. Although the vast majority of scientific community, as well as many other influential personalities, clinged together to convey the message of vaccines as a secure and well-validated prehemptive strategy to avoid some catastrophic pathologies and epidemies, clarifying that the risk of side effects is low and largely surpassed by that of infection-related complications (see here), many people are still reluctant to accept trustful scientifical evidences as a way to dissipate skepticism. In the perspective of promoting good information and avoid aberrant conducts driven by mythomania, however, the italian National Order of Biologists (Ordine Nazionale dei Biologi, ONB), seems to have preferred an "alternative", paradoxical path. 

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Harnessing the potential of gene editing-based therapies has been one of the long sought-after dreams of biology and medicine. New techniques such as CRISPR and ZFP, though still in need of being refined, have opened the possibility of manipulating genomes and, for example, target specific disease-associated genes. While the perspective of modifying organisms in order to make them less susceptible to certain conditions, either pathophysiological or infective, represents a rather fascinating scenario, many think that this approach still has to deal with our very limited knowledge of the way gene products work in the context of a complete organism, in relation with the other 21.000 protein-coding genes extimated to date, with the huge non-coding part of the genome and, quite importantly, environmental variables (a good example of this complexity is represented by the fact that less than a 2% DNA divergence accounts for the phenotypic differences existing between humans and chimps). As a matter of fact we might be able to modify human genes, but our knowledge of the full spectrum of effects exerted by a certain DNA sequence on living organisms is often scarce, and seldom predictable. It is no surprise, thus, that scientific comunity was profoundly shaken, a few weeks ago, when chinese scientist He Jiankui claimed that he had made the first couple of gene-edited twin babies carryinga mutation for CCR5 chemochine receptor that make them, theoretically, immune to HIV infection.

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A widely -though a little bit simplistic paradigm of central tolerance, in immunology, is that thymocytes undergo a process of deletion, during their differentiation, as they express a TCR that shows high affinity or avidity for MHC that load self-antigens. This mechanism helps eliminating autoreactive T cells that might unleash autoimmunity. However, the host of T cell precursors in the thymus is also the source of T regulatory cells (Treg), a central gear of the machinery that modulates and shapes the immune system. In this sense, Treg existence and features exposed all the limits of a model of central tolerance based on TCR affinity for MHC: indeed this theoretical approach could only partially explain the huge variety of T cells we see circulating, especially in light of paradoxical evidences such as that of Tregs partly sharing their TCR repertoire with that of conventional T cells, or the fact that they can be induced by self-antigen recognition. As it turns out, things are way more difficult to explain and the system that, in the thymus, decides the fate of CD4 T cells is rather convoluted, as Ludger Klein, Ellen A Robey and Cyi- Song Hsieh explained so eminently in Nature Reviews Immunology, last week.

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The cells characterizing healthy metazoa bodies are meant to share and maintain the same genome, with tissue diversity being originated by differential gene expression and alternative mRNA splicing during transcription. Few exceptions exist in this paradigm, the most prominent being that of B ant T cells, which are able to rearrange genomic DNA through somatic recombination and generate the huge variability of immunoglobulin and T cell receptor (TCR) repertoires.  

On the other hand, the brains of patients affected by neurodegenerative diseases often display mosaicism -the presence of mutations and different copies of certain genes in the tissue cells- which does not depend on mutations inherited by parents: for examples, the neurons of patients with Alzheimer's disease (AD) display more DNA and different copies of the amiloid precursor protein (APP) gene, which is one of the causes of this condition. Although this feature is common in neurodegenerative pathologies, its mechanism is basically unknown. In this sense, the paper published this week on Nature by Lee et al represents an important milestone of molecular biology and neuroscience: it provides a mechanistic base for neuronal mosaicism of patients with AD and other neurodegenerative conditions, proving that neuron can indeed perform somatic recombination (a feature that to date was thought to be exclusive of immune cells), while it also lays new ground to understand neurodegeneration.

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Brexit is possibly one of the most difficult situations ever faced by United Kingdom in recent times. Nobody has a clear prediction for what its long-term consequences are going to be for the country, should UK definitely decide to leave EU, but what has been pretty clear in these past months is that, among those who advocated Brexit, few saw the big picture and the full spectrum of the repercussion that this event would have had on the country's health, economy and, quite relevant to our cause, science.

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Starting (and hopefully, ending) a PhD studentship is undoubtedly a thrilling -though demanding- task that is meant to teach students to cope with the hard work that is at the base of a research job. As someone new to several different duties -often performed at the same time- a PhD student can underestimate the magnitude of his tasks, and be overwhelmed by them.

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Conferences & Courses

17° Corso CRNI Viva la differenza: sesso e neuroimmunologia

March 7-10, 2018 
Bergamo - Bergamo Science Center

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Encefaliti Autoimmuni e Malattie Demielinizzanti Atipiche

16 febbraio 2018
Aula Magna Giorgio De Sandre
POLICLINICO UNIVERSITARIO G.B. ROSSI - Verona

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JNIInternational Brain Research Organization
Bringing Neuroscience to the World
JNIJournal of Neuroimmunology
Studies on all branches of neurosciences covering both research and clinical problems of neuroscientific interest.

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