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In a mouse model of lymphoma, inflammasome dysfunction increases hematopoietic stem cell turnover and accelerates lymphomagenesis. Our data show that inflammasome function, through the NLRP3–ASC–caspase 1–GSDMD axis, in bone marrow stromal cells controls the rate of hematopoietic stem cell proliferation and thereby reduces premalignant to malignant transformation.
CAR T cells are engineered from a heterogeneous pool of T cells. This study shows that CAR T cells are epigenetically imprinted by the previous antigen exposure of the original T cell, which affects subsequent functional characteristics. These epigenetic differences can be used to identify genes that can be manipulated to modify function.
A healthy immune system is tolerant to self-antigens while maintaining responsiveness to foreign threats. Co-expression of the inhibitory receptors PD-1 and CD73 regulates tolerance by restricting the expansion of auto-reactive CD4+ T cells independently of thymic selection.
Pulendran and colleagues define a molecular signature that can be used to predict the durability of antibody responses to vaccination and reveal important insights into the mechanisms by which vaccines induce durable immunity.
Gabrilovich and colleagues discuss how the functional diversity of neutrophils in cancer can be ascribed to two functional states: classically activated neutrophils and pathologically activated myeloid-derived suppressor cells.
Karin and colleagues review the response of myeloid cells and innate lymphocytes to dietary cues, their cross-regulatory interactions and roles in normal and aberrant metabolic control.
Systemic lupus erythematosus (SLE) is an autoimmune disease with considerable clinical heterogeneity and diverse treatment options. A study now shows that heightened extrafollicular B cells and anti-BAFF therapy are linked to inferior responses to COVID-19 vaccines.
Inflammasomes induce pyroptosis and, through poorly defined mechanisms, promote adaptive immune responses. High-resolution imaging of the explosive morphology of pyroptosis showed that minutes before rupture, gasdermin D instructs the cell to extend filopodia. These structures mark the corpses for recognition by the antigen-sampling receptor CLEC9A on dendritic cells.
Circulating immune stimuli access the joint through fenestrated capillaries that are located at the outer edge of the synovium. This area of vulnerability is policed by interacting macrophages and nociceptor neurons that work together as a functional unit.
In this Review, Sharma and colleagues describe the current landscape of combination therapies and discuss requirements for the development of effective combination strategies.
In this Review, Herro and Grimes summarize the most recent key findings surrounding protective versus pathogenic functions of neutrophils, elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease.
Cutaneous T cell lymphoma is a rare, difficult to diagnose malignancy of T cells. Malignant T cells, together with populations of stromal cells and B cells, shape their own tumor niche for improved cancer cell survival in the skin.
Woolf and colleagues review the current evidence that immune cells could promote pain resolution and prevention through direct effects on sensory neurons and through maintaining healthy tissue innervation.
Tumor-infiltrating T cells are known to encounter chronic antigens and hypoxia, which results in exhaustion and dysfunction. New data show that lactate fermentation, a characteristic of solid tumors, promotes the uptake of lactate into T cells via the monocarboxylate transporter MCT11, which reduces the metabolic fitness and anti-tumor function of these cells, an effect that might be targeted by immunotherapy.
We generated a mouse model to investigate the mechanistic basis of inborn errors of immunity caused by heterozygous BCL11B mutation. The BCL11B mutant protein interfered with BCL11A function, impairing T cell and neuronal development. Mutant BCL11B also failed to antagonize TCF1 function, leading to aberrant natural killer cell differentiation in the thymus.
A COQ6 variant increases susceptibility to pneumococcal infection via non-bone marrow-derived cells without affecting ubiquinone synthesis, challenging traditional views on the metabolic role of COQ6 role and opening new avenues for understanding immunometabolic interactions.
PAX5 controls the gene regulatory circuit that leads to B cell lineage commitment. A detailed study shows that the stability of PAX5 protein is reduced by acetylation, and that SIRT7-dependent deacetylation is required for full PAX5 activity.
Tertiary lymphoid structures (TLS) have different stages and cellular compositions in human tumors. New data are showing the effect of neoadjuvant immunotherapy on the fate of TLS in treatment-responsive versus treatment-resistant liver cancers.
The interplay of metabolites with epigenetic programs influences CD8+ T cell fate decisions. Here, Raychaudhuri et al. show that lactate-dependent histone lactylation tunes CD8+ T cell metabolism and function by regulating epigenetic and transcriptional remodeling.
