1,720,979 research outputs found
Metabolic fuelling of proper T cell functions
No full textThe interplay of the immune system with other aspects of physiology is one of the hottest topics of the recent literature. A crucial example is the influence of metabolic cues on immune responses. It is now well accepted that upon activation, T lymphocytes take on a metabolic profile profoundly distinct from that of their quiescent and anergic counterparts; in these sense, T cell metabolism is highly dynamic and has a serious impact on the ability of T cell to grow, activate and differentiate. Specific metabolic pathways provide energy and biosynthetic precursors able to support specific T cell functions, such as effector, regulatory and memory. Here, we review the main signaling pathways that control metabolism and how the metabolic phenotypes of T cell subtypes integrate with their specific function
Metabolic fuelling of proper T cell functions
No full textThe interplay of the immune system with other aspects of physiology is one of the hottest topics of the recent literature. A crucial example is the influence of metabolic cues on immune responses. It is now well accepted that upon activation, T lymphocytes take on a metabolic profile profoundly distinct from that of their quiescent and anergic counterparts; in these sense, T cell metabolism is highly dynamic and has a serious impact on the ability of T cell to grow, activate and differentiate. Specific metabolic pathways provide energy and biosynthetic precursors able to support specific T cell functions, such as effector, regulatory and memory. Here, we review the main signaling pathways that control metabolism and how the metabolic phenotypes of T cell subtypes integrate with their specific function
B cell immunometabolism in health and disease
No full textB cells have crucial roles in the initiation and progression of many pathological conditions, and several therapeutic strategies have targeted the function of these cells. The advent of immunometabolism has provided compelling evidence that the metabolic reprogramming of immune cells can dramatically alter physiopathological immune activities. A better knowledge of the metabolic profiles of B cells can provide valuable means for developing therapies tuning defined cell pathways. Here we review the cellular and molecular mechanisms by which immunometabolism controls the physiology and pathophysiology of B cells and discuss the experimental evidence linking B cell metabolism to health, autoimmunity, and cancer. Considering that several metabolic pathways in B cells are involved differently, or even in opposite ways, in health and disease, we discuss how targeted modulation of B cell immunometabolism could be exploited mechanistically to rebalance abnormal B cell functions that have become altered in disease states
Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function
No full textThe immune system is a highly integrated network of cells sensitive to a number of environmental factors. Interestingly, recent years have seen a dramatic increase in our understanding of how diet makes a crucial contribution to human health, affecting the immune system, secretion of adipocytokines and metabolic pathways. Recent experimental evidence indicates that diet and its components are able to profoundly influence immune responses, thus affecting the development of inflammatory and autoimmune diseases. This review aims to discuss some of the main topics concerning the impact of nutrients and their relative composition on immune cell development and function that may be particularly important for regulating the balance between inflammatory and tolerogenic processes. We also highlight the effects of diet on commensal bacteria and how changes in the composition of the microbiota alter intestinal and systemic immune homeostasis. Finally, we summarize the effects of dietary compounds on epigenetic mechanisms involved in the regulation of several immune related genes
Cellular and molecular signaling towards T cell immunological self-tolerance
No full textThe binding of a cognate antigen to T cell receptor (TCR) complex triggers a series of intracellular events controlling T cell activation, proliferation, and differentiation. Upon TCR engagement, different negative regulatory feedback mechanisms are rapidly activated to counterbalance T cell activation, thus preventing excessive signal propagation and promoting the induction of immunological self-tolerance. Both positive and negative regulatory processes are tightly controlled to ensure the effective elimination of foreign antigens while limiting surrounding tissue damage and autoimmunity. In this context, signals deriving from co-stimulatory molecules (i.e., CD80, CD86), co-inhibitory receptors (PD-1, CTLA-4), the tyrosine phosphatase CD45 and cytokines such as IL-2 synergize with TCR-derived signals to guide T cell fate and differentiation. The balance of these mechanisms is also crucial for the generation of CD4+ Foxp3+ regulatory T cells, a cellular subset involved in the control of immunological self-tolerance. This review provides an overview of the most relevant pathways induced by TCR activation combined with those derived from co-stimulatory and co-inhibitory molecules implicated in the cell-intrinsic modulation of T cell activation. In addition to the latter, we dissected mechanisms responsible for T cell-mediated suppression of immune cell activation through regulatory T cell generation, homeostasis, and effector functions. We also discuss how imbalanced signaling derived from TCR and accessory molecules can contribute to autoimmune disease pathogenesis
Metabolic control of FoxP3 expression in human regulatory T cells
Full text link2015 - 2016Regulatory CD4+CD25+ T (Treg) cells play a central role in the maintenance of immune self-tolerance and homeostasis. Although Treg cells operate through multiple mechanisms, it appears that the expression of the transcription factor Forkhead-box-P3 (FoxP3) is crucial for their function. Here we describe human peripheral Treg (pTreg) cells that develop from CD4+CD25- T (Tconv) cells following suboptimal stimulation via the T cell antigen receptor (TCR). This population of pTreg cells, which we call inducible Treg (iTreg) cells, is characterized by high FoxP3 expression, strong suppressive capacity and an active proliferative and metabolic state. The development of iTreg cells tightly depends on glycolysis, which controls FoxP3 splicing variants containing exon 2 (FoxP3-E2), through the glycolytic enzyme enolase-1. Remarkably, iTreg cells suppressive activity is impaired in autoimmune diseases such as relapsing remitting multiple sclerosis (RR-MS), and associates with the reduction of FoxP3-E2 expression, secondarily to impaired glycolysis and IL-2/IL-2R/STAT-5 signalling. These results suggest a novel mechanism that links glucose metabolism to the induction of specific FoxP3 splicing variants, via enolase-1, that directly impact on human Treg cell function, in health and in autoimmunity. [edited by author]Le cellule T regolatorie CD4+CD25+ (Treg) svolgono un ruolo centrale nel mantenimento dell’omeostasi e della tolleranza immunitaria. Sebbene le cellule Treg operino attraverso diversi meccanismi, sembra che l'espressione del fattore di trascrizione Forkhead-box-P3 (FoxP3) è fondamentale per la loro funzione. Qui descriviamo le cellule Treg periferiche (pTreg) umane che si sviluppano dalle cellule T CD4+CD25- (Tconv) dopo stimolazione subottimale del recettore delle cellule T (TCR). Questa popolazione di cellule pTreg, chiamata cellule Treg indotte (iTreg), è caratterizzata da un'elevata espressione di FoxP3, da una forte capacità soppressoria e da uno stato proliferativo e metabolico attivo. Lo sviluppo delle cellule iTreg dipende fortemente dalla glicolisi, che controlla le varianti di splicing di FoxP3 contenenti l'esone 2 (FoxP3-E2), attraverso l'enzima glicolico enolasi-1. In particolare, l’attività soppressoria delle cellule iTreg è compromessa nelle malattie autoimmuni come la sclerosi multipla recidivante-remittente (RR-MS) e si associa alla riduzione dell'espressione di FoxP3-E2, secondariamente alla compromissione della glicolisi e della via di segnalazione IL-2 / IL-2R / STAT-5. Questi risultati suggeriscono un nuovo meccanismo che collega il metabolismo del glucosio all'induzione di specifiche varianti di splicing di FoxP3, attraverso l'enolasi-1, che ha un impatto diretto sulla funzionalità delle cellule Treg, sia in condizioni fisiologiche che in corso di autoimmunità. [a cura dell'autore]XXIX n.s
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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