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Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.
Pathogenic human CD4+ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.
Tissue-resident memory T cells (TRM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal TRM cells can also have key pathogenic roles in inflammatory bowel disease.
Serpins are a large family of serine protease inhibitors. Jae Jung and colleagues show that SERPINB1 serves an endogenous regulatory role for pro-inflammatory caspases by preventing CARD–CARD polymerization and, hence, inflammasome activation.
Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.
Basophils constitute <1% of peripheral blood leukocytes. Piliponsky and colleagues show that basophils serve as a critical component of antibacterial responses by secreting tumor necrosis factor at early time points after systemic infection.
Macrophages have important antitumor functions but can be evaded by tumor-expressed CD47-dependent ‘don’t-eat-me’ signals. Beatty and colleagues demonstrate that the Toll-like receptor 9 ligand CpG metabolically reprograms macrophages to overcome don’t-eat-me signals.
The tumor microenvironment is central to the immunogenicity of tumors. Ho and colleagues show that activity of the mitochondrial protein UCP2 in tumors enhances their immunogenicity through the recruitment of dendritic cells and reprogramming of this microenvironment.
ELMO1 is a protein centrally involved in controlling the engulfment of apoptotic cells. Ravichandran and colleagues demonstrate a noncanonical role for ELMO1 in the promotion of neutrophil migration and inflammatory arthritis.
Fan and colleagues show that circular RNA circPan3 controls expression of the cytokine receptor IL-13Rα1 on intestinal stem cells and, thus, the renewal of those cells in response to IL-13 derived from group 2 innate lymphoid cells.
Regulatory T cells suppress target cells through diverse mechanisms. Shevach and colleagues demonstrate that regulatory T cells in vivo strip complexes of cognate peptide and major histocompatibility complex class II from dendritic cells and thereby help to maintain immune homeostasis.
Farrar and colleagues show that thymic Treg cells are generated through two distinct developmental programs that are both required for a comprehensive Treg cell repertoire.
Using scRNA-seq analysis, Bhattacharya and colleagues identify a subset of profibrotic lung macrophages that have a gene expression signature intermediate between those of monocytes and alveolar macrophages.
STIM1 is a calcium sensor that is essential for functional lymphocyte responses. Gwack and colleagues demonstrate a calcium-independent role for STIM1 in macrophages that regulates their production of type I interferons.