Interferon-γ couples CD8+ T cell avidity and differentiation during infection

Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate

Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer

International audienceBackground : The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expression. We explored global histone modifications during TGF-β1-induced EMT in two non-small cell lung cancer (NSCLC) cell lines and tested different epigenetic treatment to modulate or partially reverse EMT.Results: Loss of classical epithelial markers and gain of mesenchymal markers were verified in A549 and H358 cell lines during TGF-β1-induced EMT. In addition, we noticed increased expression of the axonal guidance protein semaphorin 3C (SEMA3C) and PD-L1 (programmed death-ligand 1) involved in the inhibition of the immune system, suggesting that both SEMA3C and PD-L1 could be the new markers of TGF-β1-induced EMT. H3K79me3 and H2BK120me1 were decreased in A549 and H358 cell lines after a 48-h TGF-β1 treatment, as well as H2BK120ac in A549 cells. However, decreased H3K79me3 was not associated with expression of the histone methyltransferase DOT1L. Furthermore, H3K79me3 was decreased in tumors compared in normal tissues and not associated with cell proliferation. Associations of histone deacetylase inhibitor (SAHA) with DOT1L inhibitors (EPZ5676 or SGC0946) or BET bromodomain inhibitor (PFI-1) were efficient to partially reverse TGF-β1 effects by decreasing expression of PD-L1, SEMA3C, and its receptor neuropilin-2 (NRP2) and by increasing epithelial markers such as E-cadherin.Conclusion : Histone methylation was modified during EMT, and combination of epigenetic compounds with conventional or targeted chemotherapy might contribute to reduce metastasis and to enhance clinical responses

Effets in vivo et in vitro du Bone Morphogenic Protein-7 (BMP-7) sur la transition épithélio-mésenchymateuse expérimentale

11e réunion commune de la Société Francophone de Dialyse et de la Société de Néphrologie (Toulouse, 29/9 au 2/10/2009)info:eu-repo/semantics/publishe

MYUZ

INTRODUCTION One of the first things we agreed to as an editorial staff was that our university???s literary journal needed an updated title. There was nothing inherently wrong with the name Island Fox, per se, but we preferred something that might better demonstrate the joie de vivre of writing. After batting about a few names, we settled on MYUZ ??? a nod of appreciation to the nine daughters of Zeus ??? the Greek goddesses of artistic inspiration. A muse is something (or someone) every writer needs ??? an inspirational influence to whisper in their ear, to help lift their words and voice above the mundane.\ud During this past year, newspapers, television, and internet blogs have been filled with bad news ??? some of it terrifying. Here in Ventura County we were jolted by the huge loss of life in the Chatsworth Metrolink crash ??? the worst train accident in California history. We have decided to open our journal this year\ud with a non-fiction piece by Joshua Bauer that deals with this tragedy. Bauer begins his first person narrative with a group of friends getting together for a few games of bowling. The Metrolink disaster, which had happened just two days before, is not really on their radar. The story takes a dramatic turn when Katie, a young woman who had been quiet all evening, suddenly reveals the news that a friend of theirs from high school was one of the Metrolink victims. Another short story you???ll be sure to want to check out is Bishara, Avi, Always, Kristi Kellog???s narrative of what happens when a conservative Hindu boy meets a worldly Indian girl hell-bent on winning a major beauty contest. Poetry is well represented in this year???s journal, making up about one-half of the entries. Adam Piccirilli electrifies us with his love poem Arc Eyes, Sara Parker introduces us to the horrors of nursing home life in A Part of Adulthood I???d Rather Avoid, and Krista Wilbur, last year???s managing editor, takes us into the dark, blood-stained alleys of poesie noir with Kaleidoscope. Current events were popular with our submitters this year; Sara Parker comes through again, delivering a sarcastic political elbow-punch with Hooray For Proposition 8, Chris O???Neal tells us the advantages of pet ownership during a recessionary economy in Do Rabbits Dream of Electric People, and Sean Colletti???s esoteric Now Serving Number 44 will have you puzzling over its meaning. Look closely ??? the clues are there.\ud Our editorial committee offers up their own contributions, of course. MYUZ???s mamma capa, Kellie Griffin, brings us into the lives of two young friends on their way to a blood test in Transposition, Julie Fontes shows us what can happen when you meet up with your past at a downtown club in And Hearts, and Guy MacLaury illustrates the perils of beachcombing after dark in Jamaica with A Walk on the Seven Mile Beach. In addition,\ud Luis Maranan takes us into the gravity-prone forest of One Hundred Hills, there???s the aforementioned reflective non-fiction short story from Joshua Bauer ??? Spared ??? and George Morgan squeezes in a few pages with a story about cul-de-sac culture, helicopters, and Polynesian cannabis in Where the Road Ends. We broke some new ground this year, using technology in innovative ways. This is the first time the CSUCI literary journal has been published by an online publishing company: lulu.com. This will allow copies of MYUZ to be available in perpetuity. All in all we believe our readers will enjoy the writing in this year???s campus journal. It???s been a pleasure putting it together. If you have any comments, or ideas to improve the next one, please write to us at [email protected]. The MYUZ Committe

BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets

During neurogenesis, neural stem/progenitor cells (NPCs) undergo an irreversible fate transition to become neurons. The Notch pathway is important for this process, and repression of Notch-dependent Hes genes is essential for triggering differentiation. However, Notch signaling often remains active throughout neuronal differentiation, implying a change in the transcriptional responsiveness to Notch during the neurogenic transition. We identified Bcl6, an oncogene, as encoding a proneurogenic factor that is required for proper neurogenesis of the mouse cerebral cortex. BCL6 promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter. BCL6 triggered exclusion of the co-activator Mastermind-like 1 and recruitment of the NAD+-dependent deacetylase Sirt1, which was required for BCL6-dependent neurogenesis. The resulting epigenetic silencing of Hes5 led to neuronal differentiation despite active Notch signaling. Our findings suggest a role for BCL6 in neurogenesis and uncover Notch-BCL6-Sirt1 interactions that may affect other aspects of physiology and disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe