January 2012 | Volume 209, No. 1
Brief Definitive Reports
- A novel neuroprotective therapy for Parkinson’s disease using a viral noncoding RNA that protects mitochondrial Complex I activity
When fused to a rabies virus glycoprotein peptide that shuttles small RNAs across the blood–brain barrier, an HCMV noncoding RNA that protects mitochondrial Complex I activity, delivered intravenously, shows therapeutic efficacy in a rat model of Parkinson’s disease.
- RAG-induced DNA double-strand breaks signal through Pim2 to promote pre–B cell survival and limit proliferation
During IgL chain rearrangement in mouse pre–B cells, DNA breaks inflicted by RAG proteins induce Pim2 to promote cell survival and limit proliferation; thus, DNA breaks effectively stand in for the prosurvival cytokine IL-7, whose signaling is attenuated during this stage of B cell development.
- A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP
A homozygous mutation that gave rise to a stop codon in the WIPF1 gene resulted in WASP protein destabilization and in symptoms resembling those of Wiskott-Aldrich syndrome
- A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2
Mice expressing a transgene encoding the transcription factor NF-E2 in hematopoietic cells exhibit features of myeloproliferative neoplasms, including thrombocytosis, Epo-independent colony formation, stem and progenitor cell overabundance, leukocytosis, and progression to acute myeloid leukemia.
- Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients
In situ tetramer staining reveals the presence of islet antigen-reactive CD8+ T cells in pancreatic islets from deceased type 1 diabetes patients.
- Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
Early after symptom onset, HCV-specific CD4+ T cell responses are primed and detectable in patients regardless of clinical outcome, but without early antiviral therapy these T cells become exhausted or deleted in chronically infected patients.
- Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection
Loss of intracellular TRAF1 expression correlates with CD8+ T cell exhaustion and contributes to increased viral load at the chronic stage of HIV and LCMV infection, a phenotype that can be reversed by IL-7 stimulation together with 4-1BB agonist.
- Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo
P. berghei ANKA parasites deficient in schizont membrane-associated cytoadherence protein reveal a beneficial role for CD36-mediated tissue sequestration in aiding parasite growth.
- Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10–producing suppressive CD4+ T cells
Targeting antigens to the lectinlike DC-ASGPR receptor on human DCs and in nonhuman primates results in the induction of antigen-specific IL-10–producing CD4+ T cells.
- Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon
Blood monocytes differentiate into distinct colonic macrophage or dendritic cell subsets depending on the presence or absence of inflammation
- High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses
HMGN1 is a novel alarmin that signals through TLR4 and is required for LPS-induced immune responses in vivo.
- The E3 ubiquitin ligase Mule acts through the ATM–p53 axis to maintain B lymphocyte homeostasis
Genetic manipulation reveals that Mule is vital for B cell development, proliferation, and homeostasis as a result of its ability to regulate p53 and ATM.
- Gfi1b negatively regulates Rag expression directly and via the repression of FoxO1
Gfi1b negatively regulates Rag expression through direct binding to the Rag locus and through inhibition of Foxo1; mice lacking both Gfi1b and Gfi1 exhibit a block in B cell development.