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Cover Image
Cover Image
ON THE COVER
Antibodies to the transferrin receptor (TfR) are used to transport therapeutic molecules across the blood-brain barrier. Bien-Ly et al. demonstrate that high-affinity antibodies to TfR trigger internalization and lysosomal degradation of the receptor, impairing the passage of molecules into the brain. These findings help explain the proven superiority of low-affinity anti-TfR antibodies. Image depicts brain endothelial cell nuclei (green) with high-affinity anti-TfR antibodies localizing with the lysosomal marker LAMP1 (red). Art by Lewis Long (longdesign@earthlink.net).
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Brief Definitive Report
Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate
Erythropoietin suppresses non-erythroid cell fate options to induce an erythroid lineage bias at all lineage bifurcations between HSCs and committed erythroid progenitors.
Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation
The antiviral drug ganciclovir inhibits microglial proliferation and protects against disease in mice with experimental autoimmunity encephalomyelitis.
Gata3 drives development of RORγt+ group 3 innate lymphoid cells
The transcription factor Gata3 is required for the generation of group 3 innate lymphoid cells (ILC3) that protect mucosal surfaces.
Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells
Hematopoietic stem cells expressing intermediate levels of Kit have superior repopulation capacity after transplantation compared with those expressing high levels of Kit.
Article
High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias
c-Kitlo HSCs exhibit enhanced self-renewal and long-term reconstitution potential and give rise to c-Kithi HSCs that have a megakaryocytic bias.
Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants
High-affinity transferrin receptor (TfR) bispecific antibodies facilitate trafficking of TfR to lysosomes and induce TfR degradation to decrease the ability of TfR to mediate BBB transcytosis.
Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons
Quiescence acts as a safeguard mechanism to ensure survival of the HSC pool during chronic IFN-1 exposure
Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension
Reduced expression of bone morphogenetic protein receptor 2 subverts a stress granule response, heightens GM-CSF mRNA translation, and increases inflammatory cell recruitment to exacerbate pulmonary arterial hypertension.
Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid
DHA diols produced by Müller cells suppress Notch activation in endothelial cells, thereby promoting retinal angiogenesis.
2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses
Blockade of CD28 signals results in the up-regulation of 2B4 on primary CD8+ effectors and plays a critical role in controlling antigen-specific CD8+ T cell responses.
USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase
The deubiquitinase USP21 targets RIG-I for deubiquitination, thus dampening interferon production and activation of IFN-responsive genes in response to RNA viruses.
The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification
CD73 expression is induced in response to TCR ligation and identifies a population of thymocytes that are committed to the γδ T cell fate.
Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation
Memory CD8+ T cells require stronger TCR stimulation than naive cells to enter cell cycle due to reduced Zap70 activation and increased levels of protein tyrosine phosphatases.
Light chain editors of anti-DNA receptors in human B cells
Human L chain repertoire includes editor L chains that appear to regulate anti-DNA B cells and shape the B cell repertoire.
Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells
Monovalent engagement can trigger BCR signal transduction, and fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition.
