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Apart from lifestyle, environment and chance events, genetic factors have a key role in delineating the health and longevity of an individual. Research by Park et al. has now shed light on the role of mammalian GIMAP5, a longevity-assurance (LASS) gene encoding a GTP-binding protein that regulates ceramide synthesis and cellular senescence.
The transcription cofactor TLE3 interacts with RUNX3 and TCF1 to repress the transcription and chromatin accessibility of CD8+ TCM cell signature genes, while simultaneously acting as a coactivator for TBET to facilitate the expression of CD8+ TEM cell signature genes. As such, TLE3 serves as a gatekeeper of CD8+ TCM cell formation.
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.
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.
BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.
The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.
Regulatory T (Treg) cells maintain the balance between immune protection and pathology. Research has now found that intestinal Treg cells produce IL-27 to restrain TH17 cell-mediated immune responses, effectively restricting autoimmune inflammation and limiting T cell responses to certain gut pathogens.
Determining the immune crosstalk between macrophages and NK cells in bronchioalveolar lavage fluid during SARS-CoV-2 infection in macaques identifies immunoregulatory properties of NK cells and their implications for viral persistence.
S100A8 and S100A9 are cytosolic alarmins with autocrine functions that facilitate neutrophil recruitment. Rapid, transient gasdermin-D pore formation is now shown to mediate secretion of these proteins in response to E-selectin without driving pyroptosis.
Severe COVID-19 is marked by excessive inflammation that can persist after infection. The commensal yeast Candida albicans is now implicated in the acute and chronic immunopathology of COVID-19.
Hogan et al. identify a co-immunodominant influenza peptide presented in mice by MHC-E, a nonclassical class I molecule. Notably, the peptide derives from a 16-residue alternative reading frame translated by leaky ribosome scanning of the M1 mRNA and is recognized by conventional CD8+ T cells.
Immune checkpoint inhibitors provide beneficial anti-tumor immunity but risk immune-related adverse events occurring in normal tissues. Notably, selective deletion of PGLYRP1, a protein expressed by several immune cells, protects against tumor cell growth and autoimmunity.
For decades, beta-blockers have been used widely to treat cardiovascular diseases. Surprisingly, new data show how these inhibitors can also improve immunotherapy against tumors and chronic infections.
After vaccination, spike-specific CD8+ T cells play an important part in the immediate immune response to breakthrough SARS-CoV-2 infection, whereas the B cell and neutralizing antibody responses come into effect 2 weeks after infection.
Many transcription factors contain intrinsically disordered regions whose functions are not well characterized. An intrinsically disordered region in TCF-1 has now been found to have an essential function in coordinating T cell lineage commitment.
The transcription factor NFAT5 regulates T cell exhaustion, a dysfunctional state caused by chronic exposure to antigen and other signals, during cancer but not during chronic viral infection.