Volume 19 Issue 3, March 2018

Large-scale genetic and immunological profiling reveals key environmental and genetic drivers of immunological diversity within the healthy human population.

Tumor cells downregulate type I interferon responses through their delivery of immunomodulatory exosomes, which has implications for antiviral suppression in people with cancer.

The transcription factor Hoxb5 is expressed specifically in hematopoietic stem cells, yet its ectopic expression in mouse B cell progenitors induces their conversion into functional T cells in vivo.

McKinney and Smith review the metabolic exhaustion of T cells in infection, cancer and autoimmunity

Primary liver cancer, of which hepatocellular carcinoma is the most common form, is the second leading cause of cancer-related death. Heikenwalder and colleagues review the important inflammatory component underlying hepatocellular carcinoma and consider potential directions for therapy.

Cancer can be associated with alterations in innate immunity. Gao et al. demonstrate that these alterations arise from immunomodulatory exosomes released by tumors, which then dampen the production of type I interferons by macrophages.

Polymorphisms in the autophagy protein Atg16l are associated with human inflammatory bowel disease. Murthy and colleagues demonstrate that atg16l is crucial to autophagocytic degradation of the innate adapter TRIF and thereby restrains pathological over-production of type I interferons.

The presentation of antigen by germinal-center B cells to follicular T cells engenders the process of antibody affinity maturation and humoral memory. Pierce and colleagues show that TLR9 signaling in B cells antagonizes B cell–mediated antigen presentation, which leads to the enhanced generation of short-lived plasma cells and the production of lower-affinity antibodies.

Affinity maturation and positive selection occur in germinal centers. Turner and colleagues demonstrate that the RNA-binding protein PTBP1 serves an essential B cell–intrinsic role by regulating the abundance and alternate splicing of transcripts in germinal center B cells.

Wang and colleagues show that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is absent from committed B cells and T cells, can reprogram pro-pre-B cells into functional early T cell lineage progenitors.

Regulatory T (T_reg) cells have distinct transcriptional programs underpinning their suppressive functions. Benoist and colleagues use single-cell RNA-seq to describe the transcriptional landscape of T_reg cells and the effects of T cell–receptor signaling.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.