Research articles

Peanut oral immunotherapy reshapes T cell responses, suppressing allergy-associated type 2 helper T cells and boosting cytotoxic type 1 helper T cells, offering clues to long-term tolerance.

Huang and colleagues report that TIM4–AMPK signaling induces downregulation of the mitochondrial HSP90 chaperone TRAP1 in tumor-associated macrophages, thereby enhancing their immunoinhibitory function and promoting immune evasion and tumorigenesis.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

Kallies and colleagues examine the role of the chromatin regulator SATB1 in CD8⁺ T cell differentiation during viral infection and cancer. They show that SATB1 is a negative regulator of exhausted CD8⁺ T cell expansion and effector differentiation.

Coufal and colleagues generated microglia from human iPS cells to examine mechanistic roles of the transcription factor MEF2C and how these roles might relate to the autism phenotype seen following the loss of MEF2C in human microglia.

Grimes and colleagues integrate multiomic features to create a framework that allows the isolation of discrete cell states across hematopoiesis and exploit the underlying gene regulatory networks to identify lineage restriction within multilineage progenitors.

Caielli and colleagues performed single-cell RNA sequencing on blood CD4⁺ T cells from pediatric patients with systemic lupus erythematosus and healthy donors, identifying naive, memory, T_reg, proliferative and interferon-stimulated gene-high cell subsets. Follicular and peripheral helper T cells, including T_H10 cells, and cytotoxic memory cell populations were expanded, along with dysfunctional T_reg cells marked by aberrant TLR5 and FCRL3 expression, pointing to links between microbial dysbiosis and impaired immune regulation.

Joller and colleagues show that the co-inhibitory receptor TIGIT induces the expression of the tissue growth factor amphiregulin (Areg) in regulatory T cells and contributes to tissue repair in response to viral infection.

The authors report that an AS03-adjuvanted chimeric hemagglutinin-based influenza vaccine induces persistent stalk-specific serum antibody and bone marrow plasma cell responses in nonhuman primates, offering promise for broader and durable flu protection.

Pucella, Maqueda-Alfaro and colleagues distinguish three developmentally related subsets of mouse plasmacytoid dendritic cells that differ in their ability to produce type I interferon and their susceptibility to virus.

Here the authors map the dynamics of human NK cell residency and recirculation, showing that CD56^bright NK cells transiently occupy tissues and recirculate via lymphatics, whereas CD56^dim NK cells remain vascular except during inflammation.

Rudensky and colleagues demonstrate a context-dependent differential requirement for Foxp3 for T_reg cell transcriptional and functional programs.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Klein and colleagues characterize 04_A06, a new V_H1-2-encoded broadly neutralizing antibody that has marked breadth and potency against extended multiclade HIV-1 pseudovirus panels and can maintain full viral suppression in HIV-1-infected humanized mice.

Here the authors provide a deep tissue analysis of patients with autoimmune kidney diseases, identifying a conserved spatiotemporal immune program for the development of glomerular crescents and sclerosis.

DNA damage from chemotherapy can activate cGAS–STING and interferon pathways. Here, the authors show that cGAS–STING signaling is specific to DNA rich in CA repeats, whereas DNA not rich in CA repeats is detected by AIM2, resulting in opposing tumor immune responses.

Previous research has suggested that pDCs are required for an effective antiviral immune response, but direct experimental evidence to support this is lacking. Here Ngo et al. develop a pDC knockin mouse model and find that pDCs are dispensable for an antiviral immune response to mouse cytomegalovirus and may be detrimental during influenza or SARS-CoV-2 infection.

Steele et al. use single-cell RNA sequencing and spatial transcriptomics to provide an atlas of adult human skin fibroblasts in healthy and diseased human skin.

The authors spatially and functionally map innate lymphoid cells in the human female genital tract at homeostasis, uncovering tissue-specific and subset-specific distribution and functions, and rapid antiviral responses following HIV exposure.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.