ON THE COVER
Bersellini Farinotti et al. reveal a new pain mechanism generated by rheumatoid arthritis–associated autoantibodies that is dependent on immune complex formation and activation of neuronal FcγRI. The cover shows expression of FcγRI and FcγRIIb in the neurons from a wild-type dorsal root ganglion. The image was taken from the original manuscript and modified by the JEM editorial office. See page 1904.
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Brief Definitive Reports
In the livers of Plasmodium-infected mammalian hosts, the rod-shaped mosquito-stage parasites develop into spherical exoerythrocytic forms, subsequently forming the erythrocyte-stage parasites and eventually causing malaria. Here, Bando et al. identify CXCR4 as a host factor for Plasmodium liver-stage development.
The E-protein transcription factors E2A and HEB regulate thymocyte expression of the chemokine receptor CXCR4 to retain preselection thymocytes in the thymic cortex. TCR-mediated positive selection signals extinguish CXCR4 expression to allow positively selected thymocytes to migrate from the cortex into the thymic medulla.
The human CD117+ CRTH2− ILC population contains ILC precursors. Nagasawa et al. segregate this population by the mutually exclusive expression of KLRG1 and NKp46. KLRG1+ ILCs are biased toward the ILC2 lineage, whereas NKp46 clearly defines ILC3-lineage–biased cells.
We report autosomal recessive IL-18BP deficiency in a child who died of fulminant hepatitis upon infection with hepatitis A virus. Deficiency of IL-18BP leads to excessive IL-18 activity and uncontrolled IL-18–mediated hepatotoxicity in the infected liver.
CXCR5+ TCF1+ CD8+ T cells sustain responses during persistent viral infection and mediate the proliferative burst following anti-PD1 treatment. Huang et al. show that IL-27 supports rapid division of these cells by competing with type 1 interferon for STAT1, driving IRF1 expression and preventing cell death.
The complex of MCMV proteins and MHC class I evades NK cell control and drives the evolution of virus-specific activating Ly49 receptors
Železnjak et al. demonstrate that two MCMV-encoded proteins interact with MHC I molecules, forming an altered-self complex that prevents missing self recognition by increasing specificity for inhibitory Ly49 receptors. This led to the evolution of CMV-specific activating Ly49s.
A Mg2+-dependent mechanism regulates proximal T cell receptor signaling by modulating ITK activity through a low-affinity Mg2+ binding pocket in the catalytic domain. Dietary Mg2+ deprivation in mice impairs T cell activation and T cell–mediated immunity against influenza.
Uncontrolled IgE responses drive allergies and anaphylaxis. Here, Cañete et al. describe a human follicular regulatory T cell population that does not express FOXP3 and produces abundant IL-10, which limits IgE switching. These cells appear to be key regulators of atopy.
A rational strategy to achieve optimal vaccine responses is to potentiate Tfh cells and the germinal center response. This work shows the adjuvant GLA-SE enhances circulating Tfh cells and enduring antibody responses to a malaria vaccine in Tanzanian adults.
The endothelial ERK1/2 pathway plays a crucial role in the maintenance of endothelial homeostasis. Its suppression results in activation of TGFβ signaling, leading to hypertension, renal failure, fibrosis, and sudden death, findings similar to those observed in patients treated with anti-VEGF agents.
This study reveals a novel signaling function of CX3CL1: its intracellular domain controls adult neurogenesis and reverses pathological development of amyloid pathologies in Alzheimer’s mouse brains. Ectopic expression of this domain is likely a novel therapeutic strategy in humans.
This work elucidates a novel pain mechanism generated by rheumatoid arthritis–associated autoantibodies, uncoupled from inflammation, that is dependent on immune complex formation and activation of neuronal FcγRI.
Silverman et al. demonstrate that complement activation features prominently in retinitis pigmentosa in close association with activated microglia. This response mediates adaptive neuroprotection for photoreceptors by facilitating a C3-CR3–dependent clearance of apoptotic photoreceptors by microglial phagocytosis.
The authors report a mutation in the long noncoding RNA Reg1cp that induces osteogenesis via vascular induction in humans. This mutation affects angiogenesis by blocking Klf3’s repressing activity. The Klf3 antagonist Ophiopogonin D could promote CD31hiEmcnhi vessel formation and osteogenesis in osteoporosis mice.