News & Views

Chronic antigen exposure drives TOX expression in CD8⁺ T cells and is associated with an exhausted hypofunctional T cell state. By contrast, data now show that the function of TOX in CD4⁺ T cells defines the T_H1 lineage and supports the effector function of these cells.

Metabolic stress is associated with impaired immunity, yet underlying mechanisms remain unclear. Description of a xanthine-dependent antioxidant program that shields CD8⁺ T cells from ferroptosis reveals a metabolically actionable axis that control anti-tumor responses.

Disruption of lipid asymmetry is not only a consequence of cell death but also a decisive step in the formation of neutrophil extracellular traps.

A study shows that the unique pMHC repertoire of cortical thymic epithelial cells is crucial for the differentiation of cytotoxic CD8⁺ T cells, providing the TCR signaling disruption needed as thymocytes move into the medulla, where a different pMHC set is encountered.

Bacterial type III secretion systems, traditionally viewed as virulence factors, are prevalent in healthy gut microbiomes, where they deliver effectors that modulate human immune signaling and influence susceptibility to inflammatory diseases.

Variation in HLA class I signal peptides sets the strength of NKG2A-mediated education of CD56^bright natural killer (NK) cells, revealing a genetically encoded ‘set point’ for innate immune fitness and linking NK cell tuning to protection from cancer and inflammatory disease.

A dual-recombinase fate-mapping system enables the permanent labeling of T cells activated during a treatment window, providing insights into the site-specific acquisition of diverse effector functions acquired at different antigen-priming sites.

Fibroblasts and macrophages have classically been viewed as engaging in a one-way supportive relationship in which fibroblasts sustain macrophage survival. Emerging evidence now challenges this paradigm by demonstrating a bidirectional regulatory circuit in which macrophages actively restrain fibroblast activation to preserve tissue integrity.

Activation of the nucleic acid-sensing receptors TLR7 and TLR8 must be tightly regulated, as aberrant activation can result in autoimmune disease. Data now show that endogenous RNA fragments actively impose an allosteric checkpoint on receptor activation.

Poor persistence limits the efficacy of cellular immunotherapies. Three studies now show how the quiescence factor BACH2 can be exploited to improve the therapeutic potential of T cell immunotherapy.

Type 2 immunity in the gut is regulated by an interplay between epithelial and immune cells. A recent Nature paper shows that pain receptors amplify this response by promoting the differentiation of epithelial tuft cells.

GDF15 is best known for metabolic effects in managing obesity but has been implicated in nausea experienced by some pregnant women. Data now show how GDF15 attenuates adaptive immunity through a subset of neurons in the brainstem, which can increase sympathetic tone in the spleen by releasing norepinephrine that is sensed by T cells.

The identification of a new Asn332 glycan-independent anti-HIV-1 neutralizing antibody that targets the V3 epitope, together with an Asn332 glycan-deficient priming immunogen capable of inducing B cell precursors of Asn332 glycan-dependent and -independent neutralizing antibodies, redefines the V3 loop in HIV-1 vaccine development.

Comparative single-cell transcriptomic analysis identifies clonally expanded tissue-resident CD8⁺ T cells within the leptomeninges of individuals with neurodegenerative diseases. The findings suggest that this brain border region represents an active immune niche that contributes to neurodegeneration with disease-specific distinctions.

Immune dysfunction and aberrant metabolic remodeling are hallmarks of critical illness including sepsis. Metabolic adaptation of CD4⁺ T cells is now shown to contribute to immunosuppression and poor clinical outcomes in critical illness.

Distinct monocyte gene expression programs were identified in people with long COVID after mild-to-moderate COVID-19 versus severe acute COVID-19, providing evidence that immunological dysregulation after mild acute COVID-19 may be the result of distinct pathobiological pathways.

A comprehensive single-cell atlas now reveals eosinophil heterogeneity across several mouse tissues, linking distinct cellular states to tissue residency and lifespan, and offering insights into their context-dependent phenotypic and functional adaptations.

A newly identified, TGFβ-inducible decoy receptor for IL-17 family cytokines reveals a feedback mechanism that limits mucosal inflammation, linking epithelial and lymphoid cell responses through a common cytokine axis that controls IL-17-driven immunity.

The array of tissue macrophages characterized is ever-expanding, underscoring the importance of these cells in physiology and pathology. A population of specialized gland-associated macrophages termed adenophages has now been discovered that support efficient saliva secretion along with possible other immunological functions.

New data show that DNGR-1 enables type 1 conventional dendritic cells to sculpt cancer immunoediting through selective cross-presentation of F-actin-tethered neoantigens, enriching tumors for immune-evasive variants.