Volume 25 Issue 6, June 2024

How aging, immunity and cancer are related is incompletely understood. Data now show altered differentiation and loss of function of tumor-infiltrating T cells with aging. So-called T_TAD cells seem to be involved.

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.

The immunometabolism of microglia determines not only their own fate but also that of neurons and their function during aging and neurodegeneration.

Immune cells coordinate β-cell insulin secretion to regulate glucose levels and promote type I interferon production to control systemic viral infection.

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.

The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.

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.

Our work identifies previously unrecognized functional heterogeneity in tissue-resident interstitial macrophages. We have identified ten macrophage subsets, each thought to specifically contribute to recruiting and organizing cell types within tissues. Moreover, our findings suggest the diversity and division of labor extend to other macrophage populations previously considered homogeneous.

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.

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.

Rare genetic variants in UNC93B1 predispose to childhood-onset lupus via TLR7/-8–IRAK1/-4, validated with a corresponding mouse model.

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.

In this study, the authors suggest that in the lung ApoE is a checkpoint for monocyte-to-macrophage differentiation triggered by the dectin1–Card9 pathway.

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.

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.

Cancer and aging are associated with each other, but underlying mechanisms contributing to this correlation are unclear. Here the authors identify a dysfunctional T cell state that is distinct from typical T cell exhaustion and only occurs in the tumor microenvironment during later life.

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.

CAR T cells have shown great promise in treating some cancers and are now being applied to other diseases. Here the authors engineer mouse and human T cells and show that a single infusion can result in lasting remission from asthma in mice.

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.

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.

Singh and colleagues show Tigit controls the generation of germinal center-derived plasma cell precursors that give rise to long-lived differentiated progeny in the bone marrow.

Jakubzick and colleagues show that interstitial macrophages across various tissues display similar coordinated chemokine signatures in humans and mice.