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Tumor cells commonly express abnormally glycosylated glycoproteins such as MUC1. Burchell and colleagues show that tumor-specific MUC1-ST interacts with the lectin Siglec-9 on myeloid cells and induces their conversion into suppressive tumor-associated macrophages.
Craft and colleagues show that follicular helper T cells progress through transcriptionally and functionally distinct stages that provide specific signals for germinal center regulation.
The immune system tailors its responses according to the level of threat. Lemaitre and colleagues identify a novel version of the peptidoglycan receptor PGRP-LC and demonstrate that it tunes immune responses to live (threatening) or dead (harmless) bacteria.
Dysregulated inflammasome activation is associated with auto-inflammatory diseases. Chadee and colleagues show that prostaglandin E2 triggers rapid inhibition of the inflammasome component NLRP3 by the kinase PKA. Patients with the inflammatory disease CAPS who have mutations in NLPR3 escape this negative regulation.
Human Langerhans cells express CD1a, but those in mice do not, which makes determination of its function on these cells challenging in vivo. Through the use of a transgenic mouse that expresses CD1a, Winau and colleagues demonstrate that Langerhans cells use CD1a to present contact allergens and self lipid antigens and thereby worsen inflammatory skin conditions.
CD8α+ DCs are specialized at cross-presentation, but the mechanisms that bestow this ability have not been fully characterized. Cao and colleagues show that the lectin Siglec-G negatively regulates cross-presentation and that its expression is lower in CD8α+ DCs.
Holländer and colleagues provide a map of genes that are direct targets of the transcription factor Foxn1 in thymic epithelial cells and show that Foxn1 controls genes encoding products involved in thymocyte development, antigen processing and thymocyte selection.
Immunologic memory promotes faster and more-efficient responses after re-exposure to pathogens. Ahmed and colleagues characterize a subset of human B cells that arise after vaccination against or exposure to influenza or Ebola virus and contribute to the memory cell pool.
Boss and colleagues provide mechanistic insight into cell-division-coupled transcriptional and epigenetic reprogramming events during plasma cell differentiation.
B cells and follicular helper T cells in B cell follicles can act as important reservoirs for chronic infection by viruses such as HIV or EBV. Yu and colleagues show that a specialized subpopulation of cytotoxic T cells can enter the B cell follicles to eliminate such virus-infected cells.
Regulatory T cells (Treg cells) have essential roles in maintaining immunohomeostasis. Palmer and colleagues identify two distinct subsets of Treg cells with differing degrees of self-reactivity and regulatory function.
Variants of the human gene C13orf31 (LACC1) are associated with various disease risks. Kaser and colleagues identify a role for the protein encoded (called ‘FAMIN’) in regulating macrophage fatty-acid oxidation and lipogenesis.
The activating NK cell receptor KIR3DS1 has been linked to the outcome of various human diseases, yet a ligand that would account for its biological effects has remained unknown. Altfeld and colleagues establish HLA-F as a ligand of KIR3DS1, which helps to explain the widespread influence of this receptor in disease.
Autoimmunity can often be associated with prior infection. Blander and colleagues demonstrate a mechanism by which self-tolerance can be broken after the presentation of antigens derived from bacteria-infected apoptotic cells.
DNA viruses activate antiviral immune responses dependent on the adaptor STING. Shu and colleagues identify iRhom2 as a positive regulator that stabilizes STING and facilitates its vesicular trafficking from the endoplasmic reticulum to perinuclear microsomes after activation.
Under normal conditions, IgE+ memory B cells and IgE serum antibody are extremely scarce. Kitamura and colleagues demonstrate that the IgE B cell receptor has unique signaling properties that autonomously control IgE+ B cell numbers.
The kinase WNK1 is part of a pathway that controls the uptake of ions into kidney cells. Tybulewicz and colleagues show that a related pathway involving WNK1 also operates in T cells, in which it negatively regulates adhesion and positively regulates migration.
The contribution of stromal cells to the microenvironment of tumor-draining lymph nodes is poorly characterized. By comparative transcriptional analysis, Shields and colleagues find that tumors induce the stromal reprogramming of key pathways that affect the structure and function of such lymph nodes.
Sanchez-Madrid and colleagues show that CD69 associates with the amino acid transporter LAT1-CD98 to control the uptake of tryptophan and AhR-dependent secretion of IL-22 by skin γδ T cells.
Kueh, Rothenberg and colleagues describe distinct, asynchronous and stage-specific mechanisms of T cell commitment mediated by the transcription factors Notch, TCF-1, GATA-3 and Runx1.