March 2015 | Volume 212, No. 3
Brief Definitive Reports
- TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models
Jay and colleagues show that TREM2 deficiency reduces the number of macrophages infiltrating the brain and is protective against disease pathogenesis in mouse models of Alzheimer’s disease.
- Coupling of T cell receptor specificity to natural killer T cell development by bivalent histone H3 methylation
Using Ezh2-deficient iNKT cells, Dobenecker et al. show that loss of H3K27me3 at the bivalently marked PLZF promoter is an essential link between TCR specificity and iNKT development in mice.
- Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time
Jenkins et al. discover that failure of perforin and granzyme cytotoxicity by human and mouse CTLs/NK cells prolongs the immunological synapse, leading to repetitive calcium signaling and hypersecretion of inflammatory mediators that subsequently activate macrophages. Disengagement from target cells is dependent on apoptotic caspase signaling. The findings may provide mechanistic understanding for immunopathology in familial hemophagocytic lymphohistiocytosis.
- Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer’s disease
Takahashi et al. demonstrate that restoring glial glutamate transporter EAAT2 function improves cognitive functions and synaptic integrity while reducing amyloid plaques in a sustained fashion after treatment cessation.
- Targeting IL-17B–IL-17RB signaling with an anti–IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines
Treatment with a new antibody against IL-17RB blocks pancreatic cancer metastasis and promotes survival in mice.
- Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells
Ortiz et al. report the accumulation of immature myeloid cells in skin tissue of patients with inflammatory conditions, which predisposes to the development of cancer.
- Epithelial NAIPs protect against colonic tumorigenesis
Expression of NLR family apoptosis inhibitory proteins (NAIPs) protect against the development of tumors in two models of colorectal cancer. Protection appeared to be independent of NLRC4 inflammasome activation
- Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow
Liu, Nussenzweig, and colleagues track the differentiation of human progenitor cells into dendritic cells (DCs). They show that a granulocyte/monocyte/DC progenitor gives rise to a monocyte-DC progenitor that in turn gives rise to both monocytes and a common DC progenitor. The common DC progenitor produces the three major subsets of human DCs.
- Circulating precursors of human CD1c+ and CD141+ dendritic cells
The Liu and Nussenzweig groups identify the immediate precursor of CD1c+ and CD141+ dendritic cells in the circulation of healthy donors. These precursor cells (hpre-cDC) were detectable in cord blood, bone marrow, blood, and peripheral lymphoid organs.
- CD160 is essential for NK-mediated IFN-γ production
Tu et al. generated a novel CD160-deficient mouse and showed impaired NK cell–mediated tumor elimination and IFN-γ production. CD160+ NK cells are functionally distinct in secretion of IFN-γ from their CD160− NK cell counterparts.