November 2013 | Volume 210, No. 12
Brief Definitive Reports
- The cohesin complex regulates immunoglobulin class switch recombination
The cohesin complex is recruited to DNA switch regions and is required for nonhomologous end joining during immunoglobulin class switch recombination.
- A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination
The cohesin loading protein is required for nonhomologous end joining of double-strand DNA breaks
- A type I IFN–Flt3 ligand axis augments plasmacytoid dendritic cell development from common lymphoid progenitors
Type I interferon promotes the differentiation of plasmacytoid dendritic cells in part by up-regulating expression of Flt3 on common lymphoid progenitors.
- CD36-specific antibodies block release of HIV-1 from infected primary macrophages and its transmission to T cells
Antibody targeting CD36 on HIV-1–infected macrophages results in rapid retention of virions within virus-containing compartments to inhibit release and viral transmission to T cells.
- SIRPα polymorphisms, but not the prion protein, control phagocytosis of apoptotic cells
The regulation of phagocytosis previously ascribed to prion protein PrPC is found to be controlled by the linked locus encoding SIRPα.
- Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration
Loss of dual leucine zipper kinase results in attenuated JNK/c-Jun stress response pathway activation and reduced neuronal degeneration after kainic acid–induced excitotoxic seizures.
- A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis
A comprehensive structural portrait of the association between citrullination, the HLA-DRB1 locus, and T cell autoreactivity in rheumatoid arthritis.
- The skin is an important bulwark of acquired immunity against intestinal helminths
IL-4–producing basophils promote the trapping of N. brasiliensis in the skin during secondary infection, a process critical for limiting the spread of infection to the lungs.
- Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation
Bone morphogenetic protein 7 (BMP7) promotes the differentiation of Langerhans cells in the epidermis during prenatal development.
- On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells
VEGF-driven neovascularization transiently recruits Ly6Chigh monocytes, which subsequently alter their phenotype and exert angiogenic function to enlarge small vessels.
- Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders
Deletion of Ezh2 results in transcriptional repression of developmental regulator genes, derepression of oncogenic polycomb targets, and induction of MDS/MPN-like disease in mice that is exacerbated by concurrent deletion of Tet2.
- Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo
Loss of Asxl1 results in myelodysplastic syndrome, whereas concomitant deletion of Tet2 restores HSC self-renewal and triggers a more severe disease phenotype distinct from that seen in single-gene knockout mice.
- MIP-1α/CCL3-mediated maintenance of leukemia-initiating cells in the initiation process of chronic myeloid leukemia
BCR-ABL+lineage−c-kit− immature leukemia cells produce inflammatory MIP-1α/CCL3 to maintain leukemia-initiating cells and promote development of chronic myeloid leukemia.
- Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation
The diuretic drug spironolactone up-regulates NKG2D ligand expression in colon cancer cells via activation of the ATM–Chk2–mediated checkpoint pathway to enhance the antitumor function of NK cells.
- Extracellular adenosine regulates naive T cell development and peripheral maintenance
Adenosine receptor signaling inhibits TCR-induced activation of PI3K–Akt to reduce IL-7Rα expression on T cells, thereby regulating development and maintenance of naive T cells in the periphery.
- IL-2 coordinates IL-2–producing and regulatory T cell interplay
Regulation of IL-2–producing CD4+ T cell numbers is controlled by a quorum-sensing feedback loop as regulatory T cells sense the IL-2 produced.
- Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse
In T cells, PI3K activation in the periphery of the immune synapse leads to PIP3 accumulation that promotes actin polymerization in a pathway important for cytotoxic function.
- Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells
Memory B cells, unlike naive B cells, require a reduced level of STAT3 activation to differentiate into antibody-secreting plasmablasts in response to IL-10 and IL-21; however, this process requires IL-21R expression in both naive and memory cells.
- The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response
Direct class switching to IgE generates IgE+ GC cells that are highly apoptotic and do not contribute to the memory compartment, while sequential switching through an IgG+ intermediate results in the generation of long-lived IgE+ plasma cells.
- Overexpression of TLR7 promotes cell-intrinsic expansion and autoantibody production by transitional T1 B cells
Transgenic expression of TLR7 results in the expansion and hyperactivation of T1 B cells in response to endogenous RNA complexes, leading to increased autoantibody production.