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We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent...
La Crosse virus (LACV), a zoonotic Bunyavirus, is a major cause of pediatric viral encephalitis in the United States. A hallmark of neurological diseases caused by LACV and other encephalitic viruses is the induction of neuronal cell death. Innate immune responses have been implicated in neuronal damage, but no mechanism has been elucidated. By using in vitro studies in primary neurons and in vivo...
Although CD95L is required for T cell receptor (TCR)-induced cell death (TCR-ICD) in T helper 1 cells, the molecular mechanisms mediating TCR-ICD in Th2 cells are unknown. We found that death receptors were not involved in TCR-ICD of Th2 cells because blocking their cognate ligands had no effect on apoptosis of activated Th2 cells. Furthermore, we showed that caspases were not actively involved in...
DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-κB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1α. TL1A induces NF-κB activation and apoptosis in DR3-expressing...
The flk2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in flk2 were generated. Mutants developed into healthy adults with normal mature hematopoietic populations. However, they possessed specific deficiencies in primitive B lymphoid progenitors. Bone marrow transplantation experiments revealed a further deficiency in T cell and myeloid reconstitution by...
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