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Cover Image
Cover Image
ON THE COVER
ROP18 is a key virulence factor in Toxoplasma gondii. Yamamoto et al. show that ROP18 targets the endoplasmic reticulum–bound transcription factor ATF6β, resulting in its destabilization and degradation. The watercolor image is an abstraction of ROP18 expression (purple) in a T. gondii parasite. Artwork by Emilie Clark ([email protected]).
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Editorial
Review
Integrating mechanisms of pulmonary fibrosis
Pulmonary fibrosis is a complex and heterogeneous disease; a more detailed and integrated understanding of the cellular and molecular mechanisms influencing its pathogenesis will aid the design of new therapies.
Brief Definitive Report
Destruction of tumor vasculature and abated tumor growth upon VEGF blockade is driven by proapoptotic protein Bim in endothelial cells
VEGF deprivation induces Bim expression in tumor endothelial cells, and Bim is needed for anti-VEGF–driven endothelial cell death and tumor shrinkage.
Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas
Somatic STAT3 mutations present in a subset of inflammatory hepatocellular adenomas result in the generation of constitutively active STAT3 proteins that homodimerize independently of IL-6 stimulation.
HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells
HIF1α induction by mTOR represents a metabolic checkpoint for the differentiation of TH17 and Treg cells.
B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells
Bcl-6 expression in CD4+ T cells is required to generate extrafollicular antibody responses.
Article
Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation
Next generation sequencing and copy number analysis provide insights into the complexity of the CLL coding genome, and reveal an association between NOTCH1 mutational activation and poor prognosis.
E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
Deletion of E4F1 inflicts mitochondrial damage and oxidative stress on murine and human myeloid leukemia cells but not healthy macrophages.
Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies
Structure–function analysis and mathematical modeling reveal insight into the mechanisms through which conserved HIV-1 gp120 epitopes are masked in the HIV-1 envelope trimer.
Sustained antibody responses depend on CD28 function in bone marrow–resident plasma cells
CD28 signaling is essential for maintenance of long-term antigen-specific antibody production and for persistence of plasma cells in the bone marrow of mice.
CIN85 drives B cell responses by linking BCR signals to the canonical NF-κB pathway
CIN85 transduces B cell receptor signals to IKK-β, and its expression in B cells is essential for T cell–independent type II antibody responses in mice.
Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44
Hyaluronan synthase 2 and CD44 are required for severe lung fibrosis in response to bleomycin.
FoxM1 mediates the progenitor function of type II epithelial cells in repairing alveolar injury induced by Pseudomonas aeruginosa
Mice lacking FoxM1 specifically in progenitor-like type II alveolar epithelial cells exhibit defective alveolar barrier repair after microbe-induced lung injury.
Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth
Identification of a population of Foxp3-expressing suppressive macrophages.
Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope
Subimmunogenic vaccination with an agonist mimetope of insulin converts naive T cells into regulatory T cells and prevents type 1 diabetes in NOD mice.
The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice
As shown in humanized mice, a population of Vγ9Vδ2 T cells can reduce the severity and mortality of disease caused by infection with human and avian influenza viruses.
SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses
SOCS2-deficient T cells more readily produce Th2 cytokines, and SOCS2-deficient mice exhibit exacerbated atopic dermatitis and allergic airway inflammation.
ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18
Toxoplasma virulence factor ROP18 targets endoplasmic reticulum–bound transcription factor ATF6β in the host cell, leading to the detrimental loss of ATF6β through proteasome-dependent degradation.
Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii
Expression of a bacterial transporter protein in Toxoplasma gondii results in parasite susceptibility to Formidomycin, a drug targeting isoprenoid precursor synthesis.
