Volume 24 Issue 6, June 2023

In mice and humans, changes in neutrophil phenotypes and functionality during aging aggravate thromboinflammation in ischemic brain injury and determine the pathology associated with strokes. In mice, inhibition of CXCL3 signaling and rejuvenation of bone marrow offer ways of restricting brain injury and improving stroke outcomes.

Indigenous populations are disproportionately affected by COVID-19, but are rarely studied. An investigation of the immune response of Australian First Nations people to SARS-CoV-2 vaccination and infection shows a major effect of comorbidities.

Bystander activation that leads to expression of IL-9 in effector T_H9 cells is induced by a TCR-independent, STAT-dependent mechanism and may represent a new strategy for therapeutic intervention to treat T_H9-induced pathologies in vivo.

Deletion of TFAM, the master regulator of mitochondrial transcription and translation, limits germinal center reactions. Notably, TFAM affects several processes beyond bioenergetics, such as migration, signaling, somatic hypermutation and redox balance.

The US National Institute of Allergy and Infectious Diseases hosted a two-day virtual workshop on skin microbial communities and their interactions with the host immune system in health and disease. The aim of the workshop was to evaluate the current state of knowledge in the field and identify gaps, challenges, and future directions.

Many immune cell subsets move in an amoeboid fashion and do not require strong adhesive interactions with their surrounding when moving through interstitial tissue spaces. In stark contrast, we show that mast cells critically depend on integrin-mediated adhesion and interactions with the extracellular matrix to enable slow migration and site-specific positioning in tissues.

First Nations peoples of Australia have disproportionate rates of chronic comorbidities such as diabetes and renal disease. A study of COVID vaccination in First Nations peoples reveals that perturbed antibody responses can occur in individuals with comorbidities in a way strongly associated with altered IgG glycosylation patterns.

In this Review, Künzli and Masopust provide updates on our understanding of the biology of memory CD4⁺ T cells as well as key technological advances that facilitate their characterization.

Immune cells are generally considered to be able to move through tissues using nonadhesive amoeboid migration mechanics. Here, the authors show that, unlike other immune cells, mast cells do not use this method and instead are completely reliant on integrin–ECM interactions.

Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.

Becher et al. perform a head-to-head comparison of multiple severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccine prime-boost combinations and analyze the ensuing humoral and cellular responses in a large randomized cohort.

Boyman and colleagues perform phenotypic and B cell receptor sequencing analysis of memory B cell subsets in severe acute respiratory syndrome coronavirus 2-infected and subsequently vaccinated individuals up to 1 year post-infection to show that single memory B cell clones can adopt different trajectories.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8⁺ T cell responses.

Clarke and colleagues show that germinal center B cells have highly dynamic mitochondria, which are regulated by the transcription factor TFAM. TFAM activity is required to promote spatial entry into the germinal center reaction by modulating cellular motility.

CAR T cell success requires targeting tumors, but these cells can get trapped in other tissues, such as in the lungs, where they can cause pathology. Here, the authors use a loss-of-function CRISPR screen to identify regulators of CAR T cell tumor trafficking and engineer CAR T cells accordingly to overcome this limitation.

Single-cell and spatial analyses of conserved regulatory T (T_reg) cell-dependent transcriptional states of diverse accessory cell types in mouse and human lung cancer suggest rational T_reg cell targeting-based combination therapy for PD-1 blockade-resistant tumors.

Schwartz and colleagues show that T_H9 cells can respond to bystander cytokines IL-2 and IL-4 to induce antigen-independent expression of IL-9, promoting allergic inflammation. Il9 locus remodeling causes T_H9 cell instability, preventing antigen-independent activation in individuals who are nonallergic. Therapeutic targeting of the STAT5/STAT6 activation cascade may provide relief for patients with chronic allergy.