ON THE COVER
Yang et al. show that immune tolerance to self-antigens impedes the generation of some broadly protective antibodies that bind to HIV gp41. One self-antigen, kynureninase, is mutated in opossums, allowing these marsupials to generate high serum antibody titers to the corresponding HIV epitope. The cover image depicts a HIV virus (orange) with viral spikes containing gp41 subunits (blue) and Y-shaped antibodies (green). Artwork by Rachel Urkowitz (firstname.lastname@example.org).
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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 Report
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.
Immunological tolerance to self-antigen impairs humoral responses to HIV-1.
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 behaves as a tumor suppressor in AML, and Notch activation induces cell cycle arrest, differentiation, and apoptosis of AML-initiating cells.
Activating Notch with a Notch agonist peptide induces apoptosis in AML patient samples.
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.
Plasmodium falciparum infection leads to the development of protective classical and atypical memory B cell antibody responses.
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.