17 Result(s)
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Article
Role of abortive retroviral infection of neurons in spongiform CNS degeneration
RETROVIRUSES are involved in several human neurological diseases with varying pathological features1–3. Whether these diseases are due to a direct effect of the virus on nervous system cells is unknown. To gain i...
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Article
Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF
GLOBIN genes are regulated in a tissue-specific and developmental stage-specific manner, with the β-globin gene being the last to be activated in the β-gene cluster1. CACCC-nucleotide sequences, which bind multip...
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Article
Heparin is essential for the storage of specific granule proteases in mast cells
All mammals produce heparin, a negatively charged glycosaminoglycan that is a major constituent of the secretory granules of mast cells which are found in the peritoneal cavity and most connective tissues. Alt...
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Article
ICOS is critical for CD40-mediated antibody class switching
The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in regulating T-cell differentiation1,2,3,4,5. Because co-stimulatory signals are critical for regulating T-cell activation, an understa...
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Article
Restoring function in exhausted CD8 T cells during chronic viral infection
Functional impairment of antigen-specific T cells is a defining characteristic of many chronic infections, but the underlying mechanisms of T-cell dysfunction are not well understood. To address this question,...
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Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8+ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and th...
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Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy
Chronic infection with lymphocytic choriomeningitis virus promotes the establishment of a population of stem-like PD-1+ CD8+ T cells that reside in lymphoid tissues and preferentially expand when the PD-1 inhibit...
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Article
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening appr...
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Open AccessCostimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes
Metabolic syndrome is characterized by disturbances in glucose homeostasis and the development of low-grade systemic inflammation, which increase the risk to develop type 2 diabetes mellitus (T2DM). Type-2 inn...
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Open AccessA CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system
Therapies that target the function of immune cells have significant clinical efficacy in diseases such as cancer and autoimmunity. Although functional genomics has accelerated therapeutic target discovery in c...
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Article
Open AccessPD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity
Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung infla...
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Open AccessGata6+ resident peritoneal macrophages promote the growth of liver metastasis
Emerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and noth...
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Article
Open AccessPD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability
Regulatory T (Treg) cells are central to limit immune responses to allergens. Here we show that PD-L2 deficiency prevents the induction of tolerance to ovalbumin and control of airway hyperreactivity, in parti...
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Article
PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program
Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection1. Here we examine the underlying basis for this synergy. We show that PD-1 + IL-2 co...
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Article
Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance
The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been ide...
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Article
Publisher Correction: Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance
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Article
B-cell-specific checkpoint molecules that regulate anti-tumour immunity
The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cy...
