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Thomas and colleagues describe how multiple SARS-CoV-2 antigen exposures, including mRNA vaccine boosters, primary infection and breakthrough infection, shape T cell immunity.
Tussiwand and colleagues show that an uncommitted precursor expressing the lymphoid-specific factor TdT generates a large fraction of myeloid and a substantial fraction of erythro-megakaryocyte cells.
Nie et al. show that the transcription factor LRF, by upregulating expression of the integrin gene Itgb7, imprints thymic precursors of CD8αα+ intraepithelial lymphocytes for eventual seeding of the gut tissues.
Rinkevich and colleagues show that preexisting matrix is transferred by neutrophils across organs into injured sites in a manner dependent on integrin activation.
Fabry and colleagues show that cribriform plate-resident lymphatic endothelial cells respond to neuroinflammatory signals by inducing functional changes that enhance antigen capture and presentation from the cerebrospinal fluid and promote leukocyte interactions within the central nervous system.
Nahrendorf and colleagues show that B cells in the bone marrow are an important source of the neurotransmitter acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche during steady-state and emergency hematopoiesis.
RNA vaccines have been associated with high reactogenicity. Mellman and colleagues demonstrate that lipid-formulated RNA vaccines trigger IL-1 production and inflammation in humans but this pathway is dampened in mice.
Colonna and colleagues present a genome-wide characterization of DNA methylation and hydroxymethylation in innate lymphocytes and identify differentially methylated and hydroxymethylated regions between NK cells, ILC2s and ILC3s.
Tumor-associated macrophages can restrict antitumor responses. Barreira da Silva and colleagues demonstrate that the intracellular enzyme QPCTL supports recruitment of immunomodulatory macrophages to the tumor microenvironment and its targeting can enhance tumor control.
Wragg and colleagues use MHC class II tetramers and TCRβ sequencing to track clonal populations of spike-specific CD4+ cTFH cells from cohorts of convalescent individuals with coronavirus disease 2019 or SARS-CoV-2-vaccinated individuals over 15 months.
Sumida et al. resolve the human T cell transcriptional response to type I interferon stimulation at high temporal resolution and reveal a genetic network controlling coinhibitory receptor expression.
How mRNA-based coronavirus disease 2019 vaccines drive immune responses is not clear. Here the authors characterize immune responses to the BNT162b2 vaccine in mice, and show how it stimulates innate immunity, with antigen-specific CD8+ T cell responses dependent on the RNA sensor MDA5.
Although COVID-19 vaccines are proving to be generally effective, new therapeutics to neutralize SARS-CoV-2 are required. Here, the authors engineer bispecific antibodies from ACE2-blocking B38 and H4 SARS-CoV-2 neutralizing antibodies and demonstrate their superiority in mice and nonhuman primates.
Raines et al. examine the role of the PERK-mediated ER stress response in promoting and sustaining M2-like macrophages in type 2 immune response and in tumor immunity.
Sieweke and colleagues show that alveolar macrophages maintain a core gene expression program even after several months in culture and reacquire full transcriptional and epigenetic identity after transplantation into the lung.
Xue and colleagues show that the transcription factor Tcf1 preprograms a transcriptional program that supports the bioenergetic and proliferative needs of CD8+ central memory T cells in case of a secondary challenge.
Hayday and colleagues show that sustained Skint1-dependent interactions between murine intraepidermal γδ T cells and keratinocytes are required to maintain the homeostatic barrier function and phenotype of the intraepidermal γδ T cells, including their preparedness to respond appropriately to epidermal challenges.
Okazaki and colleagues develop and characterize monoclonal antibodies that co-opt T cell PD-1 activity. These antibodies can be used to ameliorate experimental autoimmune disease.
