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Articles by Simon Grassmann
LEF1 and niche factors determine T cell stemness across chronic diseases
Keywords CD8 T cells stemness differentiation niche factors autoimmunity chronic infection transcription factors LEF1 TCF1 Get full text access Log in, subscribe or purchase for full access. References 1. Philip, M. ∙ Schietinger, A. Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections Curr. Opin. Immunol. 2019; 58:98-103 2. Kaech, S.M. ∙ Cui, W. Transcriptional control of effector and memory CD8+ T cell differentiation Nat. Rev. Immunol. 2012; 12:749-761 3.
TOX drives CD4+ TH1 effector function, antitumor immunity and autoimmune pathology - Nature Immunology
Abstract TOX is a nuclear factor critical for thymic development of CD4+ thymocytes, natural killer and innate lymphoid cells. In post-thymic antigen-specific CD8+ T cells, TOX is highly expressed in settings of chronic antigen encounter such as cancer and chronic infection and required for the persistence of exhausted CD8+ T cells. The role of TOX in CD4+ T cells is less clear. Here, we show that TOX is critical for CD4+ type 1 helper T (TH1) cell differentiation.
Stepwise epigenetic signal integration drives adaptive programming of cytotoxic lymphocytes
Keywords epigenetics lymphocytes inflammation infection differentiation cell fate cytokines AP-1 factors STAT factors Get full text access Log in, subscribe or purchase for full access. References 1. Chung, H.K. ∙ McDonald, B. ∙ Kaech, S.M. The architectural design of CD8+ T cell responses in acute and chronic infection: Parallel structures with divergent fates J. Exp. Med. 2021; 218, e20201730 2. Adams, N.M. ∙ Grassmann, S. ∙ Sun, J.C. Clonal expansion of innate and adaptive lymphocytes Nat. Rev.
An IFN/STAT1/CYBB axis defines protective plasmacytoid DC–neutrophil crosstalk in Aspergillus fumigatus–infected mice
Abstract Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), a devastating infection in immunocompromised patients. Plasmacytoid DCs (pDCs) regulate host defense against IA by enhancing neutrophil antifungal properties in the lung. Here, we define the pDC activation trajectory during A. fumigatus infection and the molecular events that underlie the protective pDC–neutrophil crosstalk.
Kitlo hematopoietic stem cells exhibit distinct lymphoid-primed chromatin landscapes that enhance thymic reconstitution - Nature Communications
Abstract Hematopoietic stem cells (HSC) with multilineage potential are critical for T cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). The Kitlo HSC subset is enriched for multipotential precursors, but their T cell potential remains poorly characterized. Using a preclinical allo-HCT mouse model, we demonstrate that Kitlo HSCs provide superior thymic recovery and T cell reconstitution, resulting in improved immune responses to post-transplant infection.
Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells
Keywords NK cells MCMV TNFR2 TNF-α NF-κB signaling NIK Get full text access Log in, subscribe or purchase for full access. References 1. Vivier, E. ∙ Tomasello, E. ∙ Baratin, M. ... Functions of natural killer cells Nat. Immunol. 2008; 9:503-510 2. Bezman, N.A. ∙ Kim, C.C. ∙ Sun, J.C. ..., Immunological, Genome, Project Consortium Molecular definition of the identity and activation of natural killer cells Nat. Immunol. 2012; 13:1000-1009 3. Lau, C.M. ∙ Adams, N.M. ∙ Geary, C.D. ...
Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage
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Keywords thymus Tregs Treg cells recirculating Tregs injury thymic regeneration immune reconstitution aging amphiregulin parabiosis Introduction Robust thymic function produces a diverse T cell pool and is essential for a competent immune response.
By Andri Lemarquis, Anastasia I Kousa, Kimon Argyropoulos, Lorenz Jahn, Brianna Gipson, Jonah Pierce, Lucia Serrano-Marin, Kristen Victor, Yuzuka Kanno, Narina N. Girotra, Hana Andrlová, Jennifer Tsai, Enrico Velardi, Roshan Sharma, Simon Grassmann, Olov Ekwall, Andrew Goldstone, Jarrod A Dudakov, Susan DeWolf
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Cell Press
Verified
Neonatal T cells unleash innate powers to combat congenital cytomegalovirus infection
Innate reprogramming of T cells in congenital CMV infection In this issue of the JCI, Semmes et al. found that not only NK cells but also conventional CD8+ T cells participated in this fetomaternal collaboration (16). During congenital CMV infection, conventional CD8+ T cells upregulated NK cell markers, including Fc receptors (specifically, Fcγ receptor III: FcγRIII) and NKG2C (Figure 1).
An IFN-STAT1-CYBB Axis Defines Protective Plasmacytoid DC to Neutrophil Crosstalk During Aspergillus fumigatus Infection.
Abstract Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), a devastating infection in immunocompromised patients. Plasmacytoid dendritic cells (pDCs) regulate host defense against IA by enhancing neutrophil antifungal properties in the lung. Here, we define the pDC activation trajectory during A. fumigatus infection and the molecular events that underlie the protective pDC - neutrophil crosstalk.
IL-21 Shapes the B Cell Response in a Context-Dependent Manner
Abstract The cytokine interleukin-21 (IL-21) is a pivotal T cell-derived signal crucial for germinal center (GC) responses, but the precise mechanisms by which IL-21 influences B cell function remain elusive. Here, we investigated the B cell-intrinsic role of IL-21 signaling by employing a novel IL-21 receptor (Il21r) conditional knock-out mouse model and ex vivo culture systems and uncovered a surprising duality of IL-21 signaling in B cells.
Author Correction: Distinct developmental pathways generate functionally distinct populations of natural killer cells - Nature Immunology
Correction to: Nature Immunology https://doi.org/10.1038/s41590-024-01865-2, published online 13 June 2024. In the initially published version of this article, the middle and bottom left-hand labels in Fig. 4b were reversed and are now amended to read “Higher in ENKP_NK cells” and “Higher in ILCP_NK cells” in the HTML and PDF versions of the article. About this article Ding, Y., Lavaert, M., Grassmann, S. et al.
Distinct developmental pathways generate functionally distinct populations of natural killer cells - Nature Immunology
Abstract Natural killer (NK) cells function by eliminating virus-infected or tumor cells. Here we identified an NK-lineage-biased progenitor population, referred to as early NK progenitors (ENKPs), which developed into NK cells independently of common precursors for innate lymphoid cells (ILCPs). ENKP-derived NK cells (ENKP_NK cells) and ILCP-derived NK cells (ILCP_NK cells) were transcriptionally different.
Early antigen receptor signaling in natural killer cells alters STAT4-dependent fate decisions via epigenetic remodeling
Abstract Natural Killer (NK) cells are innate cytotoxic lymphocytes that possess features of adaptive immunity, including antigen specificity and clonal expansion. NK cells rapidly respond to cytokines released during the innate phase of viral infection and are thought to migrate from circulation into infected organs to execute their early effector functions. However, recent evidence suggests that tissue-resident NK cells are among the first responders to viral infection.
Single-Cell Profiling Reveals a Naive-Memory Relationship between CD56bright and Adaptive Human Natural Killer Cells
Abstract Development of antigen-specific memory upon pathogen exposure is a hallmark of the adaptive immune system. While natural killer (NK) cells are considered part of the innate immune system, humans exposed to the chronic viral pathogen cytomegalovirus (CMV) often possess a distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" NK cells.
Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
Highlights • Severe COVID-19 programs durable epigenetic changes and hyper-activation in monocytes • Circulating HSPC capture post-COVID-19 changes in hematopoiesis and stem cell programs • Post-COVID-19 HSPC convey epigenetic and transcriptional memory to mature progeny cells • IL-6 contributes to epigenetic reprogramming of mouse and human HSPC and myeloid cells Summary Inflammation can trigger lasting phenotypes in immune and non-immune cells.
The Neoliberal Model Is Destroying Innovation in Science
The incentives that come from the competition model of modern academia limit the freedom of researchers in a way that suppresses disruptive science. But how can we undo it? A first step is to understand why academia was transformed like this in the first place. And at the core of this transformation is the neoliberalization of science. The reigning viewpoint of neoliberal capitalism says that a (supposedly) meritocratic competition is the best way to structure society and maximize economic growth.
Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection
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Thanks for the NK cell memories - Nature Immunology
Clonal expansion and immunological memory of lymphocytes provide protective immunity against repeated pathogen exposure in mammals. New technologies are enabling the investigation of these intricate processes, focusing on human natural killer cells during human cytomegalovirus infection. A major task of the immune system is to learn from previous infections. Thus, clonal expansion and immunological memory are important features of adaptive immunity.
The Scientific World Is Still Too Obsessed With ‘Genius’
Photo: Andrew George/Unsplash Even judging by the current metrics of competition, more equal countries with broad access to a good education ensure that more people can become autonomous scientists. The number of people who have access to self-actualisation and scientific education, and not the monopolisation of resources, determines the bursts of technological progress.
Simon Grassmann - The Wire Science
The Scientific World Is Still Too Obsessed With ‘Genius’
The Scientific World Is Far Too Obsessed With “Genius”
Exploitation of junior researchers by senior scientists reeks of unfairness. But why does it matter for eureka discoveries? Since junior researchers are completely dependent on their superiors, they cannot decide what they work on, limiting their autonomy. And the unfair conditions lead many junior researchers to favor high-paying industry jobs over staying in academia. Together, this means that our current system allocates power and resources to a small number of researchers.
The Case for Proportional Representation
So argued Arthur Scargill, president of the National Union of Mineworkers, at a debate in 1986 hosted by the Socialist Society on the question of proportional representation. Far from being a technocratic or obscure issue, proportional representation (PR) and broader electoral reforms are important parts of the struggle for working-class power and democracy. Working-class and socialist organizers and leaders like Scargill have long recognized this fact.
Smart Toilets and the Endless Spread of Health Surveillance
“The average human being has a total of zero sensors, whereas your car has maybe up to 400 sensors,” a health researcher recently told NPR’s Marketplace. “We want [the human body] to be like a car dashboard, where your engine light goes on when something is off.” He may soon see his dreams come true. A bevy of so-called “smart devices” is invading the marketplace, promising to monitor us closely, intimately—invasively?—and continuously, and alert us to what ails us.
Deconvoluting global cytokine signaling networks in natural killer cells - Nature Immunology
Abstract Cytokine signaling via signal transducer and activator of transcription (STAT) proteins is crucial for optimal antiviral responses of natural killer (NK) cells. However, the pleiotropic effects of both cytokine and STAT signaling preclude the ability to precisely attribute molecular changes to specific cytokine–STAT modules. Here, we employed a multi-omics approach to deconstruct and rebuild the complex interaction of multiple cytokine signaling pathways in NK cells.
Divergent Role for STAT5 in the Adaptive Responses of Natural Killer Cells
Highlights • STAT5 is induced in NK cells by IL-12 via STAT4 during MCMV infection • NK cells require STAT5 for protection against viral infection • IL-2 and IL-15 non-redundantly drive clonal proliferation of anti-viral NK cells • IL-15 and STAT5 promote NK cell survival during the memory phase Summary Natural killer (NK) cells are innate lymphocytes with the capacity to elicit adaptive features, including clonal expansion and immunological memory.
Early emergence of T central memory precursors programs clonal dominance during chronic viral infection
Abstract Chronic cytomegalovirus (CMV) infection leads to long-term maintenance of extraordinarily large CMV-specific T cell populations. The magnitude of this so-called ‘memory inflation’ is thought to mainly depend on antigenic stimulation during the chronic phase of infection.
Why the Right Can’t Boogaloo
In far-right vernacular, the word boogaloo is code for “civil war”—and not too subtly synonymous with “race war.” It emerged in the early 2010s in far-right online networks like 4chan and came to flourish on Facebook. Its adherents are no joke.
Clonal expansion of innate and adaptive lymphocytes
Abstract One of the hallmarks of the vertebrate adaptive immune system is the prolific expansion of individual cell clones that encounter their cognate antigen. More recently, however, there is growing evidence for the clonal expansion of innate lymphocytes, particularly in the context of pathogen challenge.
Distinct Surface Expression of Activating Receptor Ly49H Drives Differential Expansion of NK Cell Clones upon Murine Cytomegalovirus Infection
Highlights • Color-barcoding enables efficient fate mapping of single lymphocytes in vivo • Clonal expansion of single Ly49H + NK cells in response to MCMV varies substantially • Inhibitory Ly49 receptors cannot account for distinct burst sizes of NK cell clones • Clonally maintained Ly49H expression levels modulate burst sizes of single NK cells Summary Natural killer (NK) cells show some features of adaptive immunity but have not been studied at the clonal level.
What I Learned Curating Presidential Theater for Obama
We drank and we worried in Saudi Arabia. The drinking was an unexpected comfort. Saudi Arabia is the only place I’ve ever been to where my baggage was sent through X-ray after I got off the plane. This was to ensure I wasn’t sullying the kingdom with booze or porn. It turned out that the Marines who guarded the consulate in Jeddah hadn’t been made to suffer such indignities, however, so they kept the cafeteria well stocked with smuggled alcohol.
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