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In this Review, Wilfahrt and Delgoffe discuss how T cells integrate nutrient sensing with activating stimuli to shape their differentiation and sensitivity to metabolites.
Xue and colleagues show that the transcription cofactor Tle3 cooperates with Runx3, Tcf1 and Tbet to limit a central memory and promote an effector memory cell signature in CD8+ T cells.
Sepsis is a global health issue in great need of effective therapies. Analysis of gene expression profiles in different tissues and at the whole-body level in mice enabled the characterization of the organism-wide host response to sepsis, which will help to build a unified mechanistic framework for the disease.
Divangahi and colleagues identify a mechanism of heterologous immunity by BCG involving cross-talk between conventional memory T cells and innate memory cells against influenza A virus infection’.
Roan et al. use Olink and single‐cell RNA sequencing (scRNA-seq) to show a dysregulated crosstalk between the cellular and humoral immune responses in individuals with long COVID 8 months postinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Callahan et al. show that GC and extra-GC sites spawn distinct MBC subsets. MBC precursors have open chromatin regions (OCRs) that will remain open in MBC progeny, with extra-GC and GC-derived MBCs having distinct OCRs and functions.
Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.
Anatomical separation exists between the generation and lodging sites of plasma cells. Transcriptome analysis of tissue-resident plasma cells provides important insights into how newly generated plasma cells acquire longevity.
Chevrier and colleagues uncovered a hierarchical cytokine circuit arising from the pairwise effects of TNF with IL-18, IFN-γ or IL-1β, which explains the organism-wide response of the host to bacterial sepsis.
The effectiveness of pneumococcal vaccines declines with age for unknown reasons. We studied the responses of older adults to the 23-valent PPSV23 and the 13-valent PCV13, identifying distinct baseline immune characteristics associated with vaccine responsiveness, including a cytotoxicity signature associated with weaker responses to PCV13.
Ravichandran et al. performed a systems immunology study to profile the responses to pneumococcal vaccines in older adults. They identified distinct baseline features that could capture responses to Prevnar and Pneumovax and sex-biased differences in Prevnar responses.
Gao and colleagues report a structure-guided chimeric antigen based on the A35 and M1 antigens of the mpox virus (MPXV) that induces strong MPXV-specific antibody responses and protection against lethal doses of vaccinia virus in mice.
Ikaros, Helios and Aiolos are transcription factors involved in lymphocyte development. Here the authors dissect the regulatory role of these Ikaros family members to understand their contribution to NK cell development and functions.
Carnosine is a mobile buffering metabolite. Here the authors link carnosine accumulation, hypoxia and intracellular pH homeostasis in cancer cells as a mechanism of tumor immune evasion via NFX1 degradation and galectin-9 activity.
Sagar and colleagues provide a comprehensive single-cell multimodal landscape of γδ T cells in various mouse tissues, unveiling site-specific adaptations and highlighting key tissue residency features of γδ T cells.
Anrather and colleagues provide a longitudinal single-cell transcriptomic atlas of brain and mouse blood following stroke, describing brain-infiltrating leukocytes, circulating leukocytes, microglia and endothelium diversity over the ischemic–reperfusion time
The alarmin IL-33 activates type 1 and type 2 immune cells via its receptor ST2 in a context-specific manner. We discovered a type 1 immunity-restricted promoter of the ST2-coding gene Il1rl1, which is located far upstream of the curated gene and is crucial for antiviral CD8+ cytotoxic T cell and CD4+ TH1 cell responses.
Terminally differentiated plasma cells reside in multiple tissues to contribute to local immunity. Nutt and colleagues examined tissue-specific differences in long-lived plasma cell lifespan and function, identifying unique transcriptional attributes in addition to the core plasma cell program.
Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.