February 2013 | Volume 210, No. 2
- Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
Hal Broxmeyer highlights the multitude of erythropoietin’s biological functions, including a novel EPO–EPOR signaling cascade involving a serpin–lysosome–cathepsin axis.
Brief Definitive Reports
- Erythropoietin-directed erythropoiesis depends on serpin inhibition of erythroblast lysosomal cathepsins
Serpina3g/Spi2A inhibits cathepsins B/L to enhance erythropoietin induced red blood cell formation.
- The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements
DNA double-strand breaks induced during Igκ recombination signal through ATM to suppress the initiation of additional Vκ-to-Jκ rearrangements.
- Signaling through C5a receptor and C3a receptor diminishes function of murine natural regulatory T cells
Blockade of C3aR/C5aR signaling in nT reg cells augments in vitro and in vivo suppression, abrogates autoimmune colitis, and prolongs allogeneic skin graft survival.
- Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-κB
Expression of the transcription factor Helios identifies thymocyte divergence during positive and negative selection.
- Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance
Macroautophagy supports central CD4+ T cell tolerance by facilitating the direct presentation of endogenous self-antigens by medullary thymic epithelial cells.
- Notch pathway activation targets AML-initiating cell homeostasis and differentiation
Notch behaves as a tumor suppressor in AML, and Notch activation induces cell cycle arrest, differentiation, and apoptosis of AML-initiating cells.
- HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders
Elevating HDL levels reduces Glut1 expression, dampens myeloproliferation, and prevents fat loss in multiple mouse models.
- Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells
Wiskott-Aldrich Syndrome protein (WASp)–mediated actin polymerization controls intracellular trafficking and compartmentalization of TLR9 ligands in plasmacytoid dendritic cells.
- Neutrophils control the magnitude and spread of the immune response in a thromboxane A2-mediated process
Neutrophil-produced thromboxane A2 controls the magnitude and spread of T cell responses to distal lymph nodes.
- Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies
Plasmodium falciparum infection leads to the development of protective classical and atypical memory B cell antibody responses.
- Iron uptake controls the generation of Leishmania infective forms through regulation of ROS levels
Iron uptake promotes hydrogen peroxide–dependent differentiation of Leishmania promastigotes into infective amastigotes.
- T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire
CD4+ T cell activation–induced Argonaute degradation and global miRNA downregulation promotes acquisition of helper T cell effector functions.