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Murphy and colleagues show that the transcription-factor complex BATF-IRF4, which recognizes AICE motifs within gene enhancers, is sensitive to TCR signaling strength and identify distinct gene targets that respond to graded doses of TCR stimulation.
‘Crown-like’ structures composed of apoptotic adipocytes surrounded by adipose tissue macrophages (ATMs) are a characteristic of obesity. Liu and colleagues show that engulfment of apoptotic adipocytes triggers an ER stress response in ATMs and drives the proinflammatory response that underlies obesity.
The gut microbiota can influence immune-cell function by the production of short-chain fatty acids. Mackay and colleagues show that diets enriched for acetate and butyrate protect non-obese diabetic mice from insulitis and diabetes progression.
Long noncoding RNAs contribute to the cell-type-specific regulation of gene expression. Fan and colleagues identify a unique conserved lncRNA, lncKdm2b, that is transcribed divergently from the Kdm2b gene and is necessary for ILC3 maintenance in the gut.
The receptor TLR9 needs to be carefully regulated to avoid recognition of self nucleic acids and ensuing autoinflammation. Saveanu and colleagues demonstrate a further level of regulation through the retention of TLR9 in IRAP+ endosomes.
Distinct transcription factors influence cell fate, including the generation of effector or memory CD8+ T cells. Goldrath, Wang and colleagues have developed a Page-Rank analysis that shows that the transcription factors YY1 and Nr3c1, which are expressed constitutively, promote the differentiation of effector cells or memory cells, respectively.
Natoli and colleagues reveal the epigenomic and transcriptional bases for gene-specific cross-repression of the cytokines IFN-γ and IL-4 in macrophages.
The intracellular sensor NLRP12 can negatively regulate inflammation. Ting and colleagues demonstrate that an absence of NLRP12 triggers a dysbiosis that feeds forward into a process of inflammation and colitis.
Immune cells give rise to the most interconnected system in the body. Meissner and colleagues perform comprehensive proteomics and secretomics to describe in detail the ‘social network’ of human immune cells and throw light on previously unknown cell connectivities.
Love and colleagues show that THEMIS enhances the TCR signaling response to low-affinity ligands by inhibiting the tyrosine-phosphatase activity of SHP-1.
B-1a B cells are a distinct subset of mature B cells that provide innate-like protection against pathogens. Busslinger and colleagues identify the transcription factor Bhlhe41 as being essential for B-1a development and self-renewal.
γδ T cells are generally understood to be innate lymphocytes. Prinz and colleagues show that human γδ T cells reconstituted after bone-marrow transplantation have a distinct repertoire that can be shaped by infection with cytomegalovirus, which suggests features of adaptive immunity.
CD8+ T cells rapidly commence transcriptional changes after antigenic encounter and priming. Yeo and colleagues find substantial transcriptional heterogeneity among responding lymphocytes, particularly at the first division, that influences cell fate.
Antigenic epitopes differ in their immunogenicity. Yewdell and colleagues show that B cell and antibody responses to influenza A virus infection display reproducible dynamic immunodominance hierarchies to viral hemagglutinin epitopes.
Antigenic drift and reassortment alters the epitopes of influenza virus. Krammer and colleagues reveal the cross-reactivity of antibody responses to viral hemagglutinin and neuraminidase in humans and several animal models, but the most prominent responses reflect ‘original antigenic sin’ to viral exposure.
Mucosal-associated invariant T cells recognize vitamin-B-derived ligands presented via the major-histocompatibility-complex-like molecule MR1. Rossjohn and colleagues demonstrate that these cells recognize a wide variety of ligands, some derived from common drugs, in an agonist or antagonist manner.
Tr1 cells have potent regulatory effects in vitro and in vivo. Kuchroo and colleagues comprehensively describe the epigenetic, transcriptional and gene regulatory landscape that is essential for Tr1 cell differentiation.
Natural killer T cells (NKT cells) are thought to originate at the double-positive stage of thymopoiesis. Taniguchi and colleagues find that a subset of NKT cells also appear earlier, at the double-negative stage, and that these give rise to liver-resident NKT cells with highly potent effector function.
FcμR serves as a receptor for soluble IgM. Baumgarth and colleagues show that intracellular FcμR constrains the surface expression of IgM. Lack of FcμR alters B cell populations and enhances autoantibody production. FcμR thereby serves as a critical regulator of B cell homeostasis.