Issues

Zenonos et al. report the development of a new therapeutic for P. falciparum malaria. A recombinant chimeric antibody targeting basigin—a receptor essential for erythrocyte invasion—inhibited parasite invasion and rapidly cleared an established blood-stage infection in vivo.

Clearance of neurotropic infections is challenging because the CNS is relatively intolerant of immunopathological reactions. Herz et al. use a model of persistent viral infection in mice to demonstrate therapeutic antiviral T cells can purge the CNS infection without causing tissue damage resulting from limited recruitment of inflammatory innate immune cells and conversion of microglia into APCs.

Maintenance of stem cell properties is associated with reduced proliferation but it is unknown whether the transition kinetics through distinct cell cycle phases influences the function of HSCs. Mende et al examine the effects of increasing two cell cycle complexes CCND1–CDK4 and CCNE1–CDK2 on the transition kinetics of human HSCs and their maintenance and functional alterations in vivo.

Rissone et al. demonstrate that adenylate kinase AK2, an enzyme mutated in reticular dysgenesis (RD) in humans, prevents oxidative stress during hematopoiesis. Using a zebrafish model, as well as induced pluripotent stem cells derived from an RD patient, they find that AK2 deficiency affects hematopoietic stem and progenitor development with increased oxidative stress. Antioxidant treatment rescues the hematopoietic phenotypes.

Chiang et al. identify GPR18 as a novel receptor for resolvin D2, and show that activation of this receptor in human and mouse phagocytes stimulates phagocytic clearance during bacterial infections and promotes organ protection

Kang et al. show that genetic or pharmacological inactivation of the enzyme phospholipase D1 (PLD1) disrupts colitis-associated intestinal tumorigenesis by suppressing the self-renewal capacity of colon cancer stem cells.

Malle et al. identify a role for nuclear factor inducing κB (NIK) in pancreatic β cell failure. NIK activation disrupts glucose homeostasis in zebrafish in vivo and impairs glucose-stimulated insulin secretion in mouse and human islets in vitro. NIK activation also perturbs β cell insulin secretion in a diet-induced obesity mouse model. These studies reveal that NIK contributes a central mechanism for β cell failure in obesity.

Organ hemorrhage represents a major complication in thrombocytopenia with potential fatal outcome. Hillgruber et al. demonstrate that neutrophil diapedesis through the endothelial barrier is responsible for the bleeding and could represent a therapeutic target in immune-thrombocytopenic patients.

Yago et al. find that neutrophils expressing a talin1 mutant that perturbs integrin activation fail to undergo chemokine-induced arrest, spreading, and migration, thus preventing ischemia–reperfusion injury.

Greenblatt et al. show that deletion of CHMP5 in osteoclasts leads to increased bone resorption coupled with exuberant osteoblast activity, resembling an early onset form of human Paget’s Disease of Bone

Koyama et al. show that GVHD markedly enhances alloantigen presentation within the mesenteric lymph nodes, mediated by donor CD103⁺CD11b⁻ DCs that migrate from the colon under the influence of CCR7. This antigen presentation imprints gut-homing integrin signatures on donor T cells, leading to their migration to the GI tract where they mediate fulminant disease.

Zou et al. identify a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development regulating TCR-stimulated ERK signaling in the Golgi.