November 2011 | Volume 208, No. 12
- 100 years of Rous sarcoma virus
In celebration of the centennial of the publication of Peyton Rous’s JEM paper on Rous sarcoma virus, this Perspective illustrates Rous’s broad and long-lasting influence on studies of tumor virology, oncogenes, and the molecular basis of carcinogenesis.
Brief Definitive Reports
- Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans
As shown by transcriptional analysis of blood samples from human volunteers, injection with synthetic dsRNA (an agonist of the TLR3 and MDA5 pattern recognition receptors) triggered up-regulation of genes involved in innate immune pathways, similar to those induced by vaccination with the efficacious yellow fever vaccine.
- Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo
Production of type I interferon in response to virus infection reduces plasmacytoid dendritic cell numbers, thus creating a negative feedback loop.
- Register shifting of an insulin peptide–MHC complex allows diabetogenic T cells to escape thymic deletion
A single amino acid shift in TCR recognition of self peptide–MHC determines whether potentially diabetogenic CD4 T cells will be purged in the thymus or have the opportunity to undergo activation in the islets of Langerhans of mice.
- REG-γ associates with and modulates the abundance of nuclear activation-induced deaminase
REG-γ, a protein involved in protein degradation, binds to nuclear AID, and REG-γ–deficient B cells contain more AID and exhibit increased immunoglobulin class switching.
- Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo
Artificially stabilizing contacts between VE-cadherin and VE-PTP reduce vascular permeability and leukocyte extravasation in vivo.
- Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity
A new mouse in which an IRES-GFP cassette is knocked-in to the Evi1 locus reveals that HSC long-term multilineage repopulating activity specifically segregates with expression of the Evi1 transcription factor.
- Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region
Human HSCs appear first in the embryonic dorsal aorta, and only later in the yolk sac, liver, and placenta; a single human AGM region HSC can generate at least 300 daughter HSCs that are retransplantable into secondary recipient mice.
- Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways
TDP-43 interacts with and coactivates NF-κB p65 in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, and an NF-κB inhibitor suppresses ALS disease symptoms and neuromuscular junction denervation in an ALS mouse model.
- Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis
Systemic and CNS-delimited inflammation triggers skeletal muscle catabolism in a manner dependent on glucocorticoid signaling.
- Th17 lymphocytes traffic to the central nervous system independently of α4 integrin expression during EAE
Th1 lymphocytes preferentially infiltrate into the spinal cord during EAE via a VLA-4–mediated mechanism while Th17 lymphocyte infiltration is dependent on LFA-1 expression.
- In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates
Administration of an ICAM-1–specific antibody arrests dendritic cells in a semi-immature state and facilitates antigen-specific T cell tolerance to islet allografts in humanized mice and Rhesus monkeys.
- Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice
Regulatory T cells generated by allostimulation with dendritic cells, transforming growth factor β, and retinoic acid stably express Foxp3 and can suppress even ongoing GVHD in mice.
- Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers
Selective ablation of follicular dendritic cells in mice results in disorganization of primary follicles and dispersal of B cells out of splenic germinal centers.
- Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells
CCR5-binding chemokines produced in the draining lymph node after vaccinia virus infection guide naive CD8+ T cells toward DCs and away from the macrophage-rich zone, thereby facilitating optimal CD8+ T cell activation and cytokine production.
- MHC class I–specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice
In a manner partially independent of activating Fcγ receptors, antibody-mediated production of complement component C5a and recruitment of macrophages elicit transfusion-related acute lung injury in mice.
- IGSF4 is a novel TCR ζ-chain–interacting protein that enhances TCR-mediated signaling
The expression of cell surface molecule, IGSF4, on human and mouse T cells associate with the TCR ζ-chain and colocalizes to the c-SMAC to enhance cytokine production and adhesion to APCs.