April 2016 | Volume 213, No. 4
- Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design
Rappuoli et al. illustrate how new breakthroughs in the field of human immunology can be combined with insights from structural and computational biology for the rational design of novel broadly protective immunogens, potentiating the development of new vaccines against infectious diseases that still present an important unmet medical need.
Brief Definitive Report
- Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia
Boutzen et al. show that the IDH1 mutation and its oncometabolite, (R)-2-hydroxyglutarate, dysregulate downstream target pathways of myeloid-specific TFs, especially CEBPα, priming mutant IDH1-R132H AML blasts to the granulomonocytic lineage.
- Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation
Patzke et al. create human embryonic stem cell–derived neurons that enable the generation of conditional loss-of-function mutations of L1CAM. Deletion of L1CAM impairs axonal elongation, dendritic arborization, and action potential generation.
- Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation
Nussenzweig et al. use a novel mutant mouse lacking MHC class II expression on conventional dendritic cells (cDCs) to demonstrate the importance of cDCs in the maintenance of intestinal homeostasis.
- Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging
Tang et al. report that dietary restriction increases hematopoietic stem cell quiescence and their repopulation capacity during aging but impairs hematopoietic stem cell differentiation into lymphoid lineages and inhibits proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function.
- Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist
Jang et al. show that eosinophils in the small intestine can suppress Th17 cell differentiation through the secretion of the IL-1 receptor antagonist.
- The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation
Langlais et al. identify and characterize the IRF8/1 regulome, demonstrating a critical implication of its constituents in myeloid cell function, response to infections, and pathological inflammation.
- Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA
Masuda et al. show that Arid5a regulates the fate of naive CD4+ T cells to pro- or antiinflammatory T cells through selective stabilization of Stat3 mRNA under Th17-polarizing conditions.
- NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells
de Valle et al. show that, with age, NFκB1-deficient B cells spontaneously secrete IL-6 and cause a multiorgan autoimmune disease.