Volume 21 Issue 6, June 2015

In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell–mediated immunopathology in hepatitis B virus infection.

Atherosclerosis is the primary cause of heart attacks and strokes and is caused by a chronic inflammatory response in the coronary and carotid arteries. A new study shows that smooth muscle cells within atherosclerotic plaques can change phenotypes to become macrophage-like cells, thereby revealing the remarkable plasticity of these cells.

Tissue-resident memory T cells (T_RM cells) protect against recurrent or renewed infection in barrier tissues such as skin and mucosa. A new study sheds light on the clonal origin of T_RM cells and demonstrates a crucial role for tissue-embedded T cell memory in contact hypersensitivity in skin.

A new study identifies recurrent mutations in the purine biosynthesis gene phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in relapsed acute lymphoblastic leukemia (ALL). This work highlights the importance of this pathway in the pathogenesis of relapse and suggests an approach to predicting and circumventing resistance in ALL.

The study describes the use of integrative approaches to search for candidate therapeutic targets for DIPG, and the identification of an HDAC inhibitor as a potential treatment strategy

A mutation conferring resistance to novel irreversible EGFR inhibitors is identified in cell-free plasma DNA from lung cancer patients.

The authors uncover new mutations in an enzyme from the purine synthesis pathway that cause resistance to leukemia therapy, and reveal a new mechanism by which they affect drug metabolism.

Cyclophilin A, secreted by bone marrow endothelial cells, acts as a chemotactic factor for myeloma cells, which helps explain their homing to the bone marrow and suggests a potential new therapeutic strategy.

Crystal Mackall and colleagues report that antigen-independent signaling of chimeric antigen receptors (CARs) causes T cell exhaustion and reduced therapeutic efficacy of CAR T cells that can be overcome by incorporating the 4-1BB costimulatory domain into the CAR.

Pallett et al. report that myeloid derived suppressor cells expand, home to the liver, and inhibit T cell-mediated liver damage in chronic hepatitis B virus infection.

The small molecule Bis-T-23 targets actin polymerization to improve renal morphology and function in several mouse models of kidney injury and disease.

Deletion of the transcription factor Irf5 in macrophages leads to expansion of the subcutaneous fat depot but restriction of the visceral fat during obesity, resulting in improved insulin sensitivity

The miR-200 family of miRNAs is upregulated in diabetes and leads to the apoptosis of pancreatic beta cells, while its knockout prevents this pathology

A high percentage of smooth muscle cells in atherosclerotic lesions lose expression of smooth muscle marker proteins and acquire the phenotype of other cell types, a process of functional importance in lesion pathogenesis that is controlled by the transcription factor KLF4.

Metabolic changes induced by hypoxia and extracellular ATP, acting through the transcription factors HIF1-α and AHR, regulate the differentiation of type 1 regulatory (T_reg1) cells.

Following skin immunization a common naïve T cell precursor gives rise to resident and central memory T cells, which mediate rapid and delayed skin immune responses, respectively.