ON THE COVER
Teams led by Murphy and Nussenzweig designate Zbtb46 as a transcription factor that specifically marks the conventional dendritic cell (cDC) lineage. The groups present new mouse models that will facilitate visualization and specific depletion of cDCs and their committed progenitors. Original image shows Zbtb46 (green), B220 (magenta), and CD169 (blue) in skin-draining lymph nodes of mice with a GFP cassette inserted into the Zbtb46 locus. Artwork by Joshua Graver (firstname.lastname@example.org).
See pages 1053, 1135, and 1153
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Classical dendritic cells as a unique immune cell lineage
Marking and manipulating the cDC lineage.
Unstressing intemperate models: how cold stress undermines mouse modeling
Chris Karp discusses the negative impact of cold stress on mouse models of disease.
Brief Definitive Report
DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions
Genetic inactivation of the genes encoding several low-fidelity DNA polymerases indicates that DNA polymerase ζ inserts tandem double-base substitutions in the immunoglobulin variable region in mouse B cells.
Female mouse fetal loss mediated by maternal autoantibody
In mouse models of systemic lupus erythematosus, antibodies that cross-react with double-stranded DNA and the NR2A subunit of the NMDAR cause apoptosis of NR2A-expressing neurons within the brainstem of developing female fetuses, resulting in a gender bias.
Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization
A heavy chain–only antibody isolated from a llama repeatedly immunized with trimeric HIV-1 Env neutralizes 96% of tested HIV-1 strains.
Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation
EGFR requires ADAM17 activity to preserve skin barrier homeostasis.
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors
Systemic and intrathecal administration of derivatives of a nonpsychoactive component of marijuana significantly suppresses chronic inflammatory and neuropathic pain, without causing analgesic tolerance, in several rodent models.
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages
The zinc finger transcription factor Zbtb46 specifically marks cDCs and their committed precursors and, when overexpressed in BM progenitors, promotes cDC development at the expense of granulocytes.
Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage
The zinc finger transcription factor zDC is uniquely expressed by the cDC lineage among immune cells, and the insertion of diphtheria toxin receptor cDNA into the zDC locus allows specific ablation of the cDC lineage in mice.
Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages
Langerhans cell precursors initially arise from yolk sac progenitors, but are later superseded by fetal liver monocytes.
Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung
In the mouse lung, dendritic cells in the alveolar region but not the airway extend dendrites and take up antigen; antigen-loaded alveolar DCs then move to and accumulate in the airway where they encounter T cells.
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2
After encounter with its ligand, PD-1 translocates into TCR microclusters, where it transiently recruits SHP2 and suppresses phosphorylation of TCR signaling components and TCR-driven stop signals.
Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo
After transendothelial cell migration, neutrophils actively crawl along pericyte processes before exiting the venular wall via selected gaps between adjacent pericytes.