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Dendritic cells experience cell shape changes while migrating within the complex physical environment of tissues. Sensing of these shape changes modifies their migratory properties and imprints these cells with immunoregulatory properties.
Genetic lineage tracing and progenitor and multilineage fate mapping after single hematopoietic stem cell (HSC) transplantations identify two distinct HSC-progenitor trajectories for the replenishment of platelets in mice. These pathways include a slower multilineage pathway and a faster platelet-restricted or biased pathway, initiated by distinct and non-hierarchically related HSCs.
This work identifies two rare genetic variants of UNC93B1 that contribute to the development of childhood-onset lupus. Mice that expressed one of these variants developed a lupus-like disease. UNC93B1 is known to regulate the localization of Toll-like receptors (TLRs) to the endosome, and UNC93B1 variants resulted in enhanced responses to TLR7 and TLR8 agonists.
Here the authors show that BTLA on effector T cells interacts with HVEM on other immunosuppressive cells in the tumor microenvironment. The authors also present evidence that overcoming this checkpoint can ehance CAR T functionality.
Structure-guided protein design enables germline-targeting immunization strategies to generate broadly neutralizing antibodies against MPER, a region of the HIV envelope glycoprotein that is functionally important and highly conserved, but a challenging target for antibody responses.
Batista, Schief and colleagues use a series of germline-targeting immunogens in knock-in mice expressing heavy chain sequences derived from the HIV broadly neutralizing antibody 10E8 to characterize the requirements of 10E8 B cell precursors for entry and maturation in the germinal center.
Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.
Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf− hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf+ stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.
Chronic antigen exposure promotes terminal exhaustion of T cells. Here the authors show a role for TCR stimulation in preserving progenitor exhausted T cells and highlight their TCR-dependent self-renewal during antitumor responses.
Immune cells coordinate β-cell insulin secretion to regulate glucose levels and promote type I interferon production to control systemic viral infection.
Sestan et al. find a conserved mechanism during systemic viral infection in which γδ T cells produce IFNγ to increase pancreatic insulin secretion, lowering blood glucose and then enhancing type I interferon-mediated protection against viral infection.
Segal and colleagues identify a population of immature neutrophils as having regenerative properties on injured neurons and being capable of inducing axon regeneration. These findings suggest potential strategies for restoring lost neurological functions in central nervous system disorders.
Woolf and colleagues use single-cell transcriptomics to determine the gene signature of infiltrating immune cells and potential cell–cell interactions between receptors, ligands, ion channels and metabolites expressed on immune cells and sensory neurons in three models of pain.
CAR T cell technology is being extended beyond the treatment of cancer. New data show that it might also treat allergic asthma, with a single infusion sufficient to prevent pathology for over a year in mice.