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LAG-3 is a T cell inhibitory receptor with a lot of promise as a target for immunotherapy, but considerable research will be needed to fully understand the nuances of this receptor and how best to target it, as outlined in this Perspective.
Susceptibility to respiratory pathogens is increased during early life, yet children can mount highly effective immune responses to novel pathogens in the absence of a fully developed immune system. We found that bronchus-associated lymphoid tissue (BALT) develops in the lungs early in life and supports germinal center formation and B cell differentiation to produce antibodies specific for respiratory pathogens, revealing a mechanism for immune protection in an as-yet-undeveloped immune system.
Delineation of the steps that lead to immune-related adverse effects indicates that checkpoint-mediated suppression of autoreactive T cells occurs within peripheral target tissues rather than at the point of lymph node activation.
The mechanisms by which TH17 cells can either protect barrier tissues or initiate autoimmunity remain unknown. Here we identify the transcription factor EGR2 as a key determinant of TH17 cell pathogenicity. EGR2 was found to govern TH17 cell migration, regulate the expression of pathogenicity-associated genes, and facilitate the recruitment of other immune cells in the central nervous system.
Fibrosis, defined by the excess deposition of structural and matricellular proteins in the extracellular space, underlies tissue dysfunction in multiple chronic diseases. Bhattacharya and Ramachandran provide a review of recent advances in our understanding of the immunology of human fibrosis.
Tumor cells exploit G-protein-coupled receptor (GPCR) signaling networks to promote angiogenesis, grow and metastasize. We show that tumor cells leverage a GPCR–Gαs–protein kinase A (PKA) signaling axis to polarize CD8+ T cells into a dysfunctional state, thereby limiting the tumor infiltration and cytotoxic function of these cells and reducing the efficacy of current immunotherapies.
Despite the absence of MHC class II molecules on tumor cells, stem-cell-like CD4+ T cells specific for tumor neoantigens can mediate profound antitumor effects by licensing antigen-presenting cells and augmenting antitumor CD8+ T cells in the tumor microenvironment and draining lymph nodes.
Confusion exists as to whether transitional dendritic cells are a bone fide subset or just a transitional state, as the name indicates. New data are complicating matters further by showing some interesting heterogeneity in these cells.
CD8+ virtual memory T cells have been studied mainly for their antimicrobial functions but it seems that their descendants can contribute to inflammation and hair loss in the context of alopecia areata.
Nimmerjahn and colleagues review posttranslational modification of immunoglobulins and how these posttranslational modifications influence antibody effector function. Furthermore, they discuss the implications of immunoglobulin posttranslational modifications when designing therapeutic antibodies for various clinical indications.
Naive B cells activated during infection enter the germinal center (GC) reaction, in which high-affinity antibodies are generated. A new study has uncovered a distinct metabolic requirement for B cells poised to undergo the GC reaction, whose activation required lactate dehydrogenase A-dependent aerobic glycolysis.
Buggert and colleagues provide a broad picture in this review of circulating and tissue-resident memory CD8+ T cells, which are ultimately responsible for effective immune surveillance.
We identified an abundant macrophage population with a distinct transcriptomic signature in the murine mammary gland and milk during lactation. These macrophages are monocyte-derived, depend on colony-stimulating factor (CSF-1) and reside adjacent to alveoli. Human milk also contains macrophages comprising three subsets with a partial resemblance to the murine counterparts.
COVID-19 vaccines have been successful, but their duration and level of protection could be improved to cover all SARS-CoV-2 variants. A self-assembling enveloped virus-like particle vaccine combining features of mRNA and protein vaccines might provide a way forward.
Single-cell RNA sequencing distinguishes subsets of fibroblastic reticular cells and predicts pathways that support immune function via crosstalk with lymphocytes.
Extravasation of blood into the brain and activation of innate immune cells are hallmarks and therapeutic targets in neurological diseases. We show that specific blood proteins induce distinct receptor-mediated gene programs in microglia and that the blood coagulation protein fibrin has a causal role in pathogenic innate immunity in models of neurological diseases.
Presentation of signal peptides by HLA-E to natural killer cells prevents cell lysis via interactions with the inhibitory CD94–NKG2A receptor. A study now reveals an unexpected level of sophistication and heterogeneity in this receptor–ligand interaction.
Devant and Kagan review the biochemical and cell biological mechanisms that control gasdermin D pore-forming activity and its diverse downstream immunological effects.
