Volume 18 Issue 5, May 2017

IRE1α is a stress sensor that is activated by a high-fat diet. In adipose-tissue macrophages, it serves as a major switch toward pro-inflammatory M1 polarization and thereby contributes to obesity and associated diseases.

The immune system employs a multitude of molecules, cells and organs that act together throughout the entire body to guard human health. Much like in a social network, immune cells can exert full functionality only through effective collaboration and communication.

The transcription factor IRF4 acts as a 'rheostat' for TCR signaling. Discrete levels of IRF4 can activate distinct transcriptional programs in T cells due to binding sites of variable affinity in groups of target genes.

The short-chain fatty acids (SCFAs) acetate and butyrate, which are released from specialized diets by gut microbes, protect non-obese diabetic (NOD) mice against insulitis and slow the progression of diabetes.

O’Neill and colleagues review the role of mitochondria dynamics and energetics in immunity and inflammation, in innate and adaptive immune cells.

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.

‘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.

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.

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.

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.

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.

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.