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LAG3 inhibits T cell activation, but exactly how it does so has been unclear given a lack of structural information. Here the authors provide the crystal structure of the human and mouse LAG3 ectodomains, showing how they interact with known ligands and antibodies.
Shi and colleagues describe a subset of erythroid precursors with immune characteristics that can be isolated from the yolk sac to the adult bone marrow stages during human ontogenesis.
Goldrath and colleagues define the diversity of gene expression and genome accessibility in mouse CD8+ TRM cells in distinct tissues and identify molecules critical forgeneration of CD8+ TRM cells in response to acute viral infection.
Lanzavecchia and colleagues use single-cell B cell receptor sequencing to examine the clonal structure, stability and dynamics of the B cell repertoire and the relationship between memory B cells and newly generated plasma cells in humans.
Skin Treg cell crosstalk with hair-follicle stem cells (HFSCs) can control hair regrowth. Here the authors show that glucocorticoid receptor signaling in skin Treg cells induces TGF-β3, which in turn facilitates HFSC proliferation.
Vahedi and colleagues show that TCF-1 promotes T cell development by minimizing the spatial distance between regulatory elements that are located within insulated neighborhoods in progenitor cells and are required for the expression of T cell genes.
Extracellular microenvironments are more acidic upon tissue damage or in tumors. Xavier and colleagues identify a role for the pH-sensitive, G protein-coupled receptor GPR65 in multiple aspects of immune cell lipid metabolism, disruption of which leads to chronic inflammatory responses.
A broadly neutralizing antibody (bnAb) response is required to combat SARS-CoV-2 variants of concern (VOCs). The authors isolated and characterized a large panel of sarbecovirus bnAbs from vaccinated individuals who had recovered from COVID-19, finding that many of these antibodies were able to neutralize all VOCs, including Omicron, and demonstrate prophylaxis in mice infected with diverse sarbecoviruses.
Breed et al. identify a subset of thymic SIRPα+ cDC2 dendritic cells that express CD301b, induced by type II cytokines, and high amounts of MHC-II. They find that the deletion of these cells can alter thymic CD4-single-positive repertoires, suggesting that they contribute to thymic tolerance.
Single-cell RNAseq during initiation and progression of mouse glioblastoma reveals a dynamic immune microenvironment transitioning from pro-inflammatory microglia in early tumors towards an infiltrating macrophage and suppressor cell-centric immune landscape in late-stage tumors.
Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.
Liston and colleagues design a gene-delivery system to specifically target astrocytes in the central nervous system to express IL-2 and thereby expand/maintain Treg cells to suppress neuroinflammation.
Exhausted T cells are associated with inefficient viral clearance, tumor immunity and response to immunotherapy. Here the authors show CD8+ T cells in the pancreatic islets have a LAG3-promoted ‘restrained’ phenotype resembling exhausted cells but maintain effector functions, and LAG3 expression limits pathology in the nonobese diabetic mouse model of type 1 diabetes.
Liang and colleagues show that the ORF45 protein from the Kaposi’s sarcoma-associated herpesvirus activates NLRP1 by binding to its Linker1 region through a mechanism distinct from the previously described, host protease DPP9-dependent mechanism of NLRP1 activation.
How the immune system responds to epithelial cancers beyond neoantigen-driven adaptive immunity is poorly understood. Kansler et al. reveal an innate immune surveillance response mediated by cytotoxic ILC1 sensing of cancer cell-expressed IL-15.
How fibrosis and inflammation are integrated is not entirely clear. Here the authors show that profibrotic proximal tubular cells in the kidneys recruit basophils and activate them to produce interleukin-6 and drive TH17 cell responses.
Around the world, governments are urging populations to receive a third COVID-19 vaccine dose. Here, the authors compare immunogenicity, reactogenicity and effectiveness of a third dose versus the second dose of the BNT162b2 vaccine in a large group of healthcare workers in Israel.