Apoptotic cells promote circulating tumor cell survival and metastasis.

During tumor progression and especially following cytotoxic therapy, cell death of both tumor and stromal cells is widespread. Despite clinical observations that high levels of apoptotic cells correlate with poorer patient outcomes, the physiological effects of dying cells on tumor progression remain incompletely understood. Here, we report that circulating apoptotic cells robustly enhance tumor cell metastasis to the lungs.

Regulatory T Cells Maintain Selective Access to IL-2 and Immune Homeostasis despite Substantially Reduced CD25 Function.

IL-2 is a critical regulator of immune homeostasis through its impact on both regulatory T (Treg) and effector T cells. However, the precise role of IL-2 in the maintenance and function of Treg cells in the adult peripheral immune system remains unclear. In this study, we report that neutralization of IL-2 in mice abrogated all IL-2R signaling in Treg cells, but was well tolerated and only gradually impacted Treg cell function and immune homeostasis.

Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against .

The live attenuated strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination.

Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity.

Although the signaling events that induce different forms of programmed cell death are well defined, the subsequent immune responses to dying cells in the context of cancer remain relatively unexplored. Necroptosis occurs downstream of the receptor-interacting protein kinases RIPK1 and RIPK3, whose activation leads to lytic cell death accompanied by de novo production of proinflammatory mediators. Here, we show that ectopic introduction of necroptotic cells to the tumor microenvironment promotes BATF3 cDC1- and CD8 leukocyte-dependent antitumor immunity accompanied by increased tumor antigen loading by tumor-associated antigen-presenting cells.

Deletion of Specific Sphingolipids in Distinct Neurons Improves Spatial Memory in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and a concomitant loss of synapses and cognitive abilities. Recently, we have proposed that an alteration of neuronal membrane lipid microdomains increases neuronal resistance toward amyloid-β stress in cultured neurons and protects from neurodegeneration in a mouse model of AD. Lipid microdomains are highly enriched in a specific subclass of glycosphingolipids, termed gangliosides.