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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.
Löhning and colleagues identify an alternative promoter for the Il1rl1 gene that drives IL-33 receptor expression in cytotoxic T cells and T-helper 1 cells
The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8+ T cell clonotypes.
Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.
Expressing chimeric antigen receptors (CARs) in macrophages has led to promising results in preclinical and clinical work. Now, induced pluripotent stem cells have been combined with a second-generation CAR to achieve macrophage rewiring and to broaden the applicability of the approach to solid malignancies.
T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8+ CAR-T cells and the bifurcation of stem-like CD8+ CAR-T cells into effector and exhausted subsets, respectively.
We describe a system for introducing guide RNAs (gRNAs) to Cas9-expressing hematopoietic stem cells, which are used to generate mice with gene knockouts in the immune system. By using different gRNA-containing vectors and Cas9-expressing mice, we created systems for knockout of single genes or pairs of genes constitutively or inducibly.
BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.
Mouse macrophages express specialized genes particular to the organs they inhabit, but whether the same applies in humans is unclear. In human peritoneal fluid, we identified many macrophage phenotypes, including two specialized macrophage types that corresponded to distinct mouse peritoneal macrophages. However, their abundances were markedly different between species.