Volume 15 Issue 12, December 2014

Physician scientists bridge the gap between biomedical research and clinical practice. However, the continuing decrease in number of people who choose this career path poses a threat to the advancement of biomedical science and the translation of research findings to clinical practice.

The combination of machine-learning tools and mass-cytometry measurements of more than 30 protein markers per cell comprehensively maps cell identity in the heterogeneous myeloid cell system and reveals the global effect of deletion of the gene encoding the receptor for the growth factor GM-CSF.

Humans deficient in the adaptor MyD88 or the kinase IRAK4 suffer from primary immunodeficiency. Blood cells from these patients show defective induction of specific subsets of genes after exposure to microbial stimuli in vitro.

Chitinase-like proteins are associated with type 2 immune responses and the 'wound-healing' pathway, but their role has remained unclear. Studies have now highlighted their contribution to IL-17 production and their link to neutrophil activity required for the control of helminth infection.

Vesicular stomatitis virus, a single-stranded RNA virus, triggers activation of the serine-threonine kinases RIP1 and RIP3, which damages mitochondria by activating the GTPase DRP1. This results in excessive production of reactive oxygen species and subsequent activation of the NLRP3 inflammasome.

Type 2 immune responses are often associated with the expression of chitinase-like Ym proteins, but their role is unclear. Allen and colleagues show that Ym1 and Ym2 act on γδ T cells to increase their expression of IL-17A and enhance the recruitment of neutrophils.

The mechanisms by which viruses activate the NLRP3 inflammasome remain unclear. Zhou and colleagues show that RNA viruses initiate a RIP1-RIP3 complex that drives mitochondrial damage and activation of the NLRP3 inflammasome independently of necrosis.

People with loss of function of MyD88 or IRAK4 have a surprisingly limited altered phenotype. Chaussabel and colleagues use a systems approach to identify defined signaling modules that are altered in such people.

Activated CD8⁺ T cells must 'choose' between the terminal effector cell fate or the memory precursor cell fate. Amsen and colleagues find that the cell surface receptor Notch controls this 'choice'.

Autophagy has essential roles in cellular energy mobilization and homeostasis, but its role in T cell memory formation is remains poorly understood. Ahmed and colleagues demonstrate that autophagy is critical for the survival of cytotoxic memory cells.

miRNAs 'tune' gene expression to orchestrate cell activity. Ansel and colleagues show that miR-19 modulates T_H2 cytokine production by targeting T_H2-specific as well as general T cell–activation pathways.

The role of the repressors Bach1 and Bach2 in early B cell development is unclear. Igarashi and colleagues have now found these Bach factors directly repress various myeloid genes in common lymphoid progenitors to restrict a B cell lineage fate.

Myeloid cells show great phenotypic and functional diversity. Newell and colleagues use mass cytometry with a panel of 38 mouse myeloid markers to describe myeloid cell phenotypic diversity in unprecedented depth within eight different tissues.