A lineage of myelolymphoblastic innate cells unmasked by inactivation of mTOR complex 1
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ABSTRACT: Blockades in hematopoiesis deprive the host of vital blood cells and frequently cause leukemia. Here we show that inactivation of mTORC1 in hematopoietic stem cells by deletion of Raptor unmasked a cell type, hereby called myelolymphoblastic innate cell (MLIC) based on unique gene expression signature, cell surface markers, morphology and functions. The MLICs are CD11b(+)Gr-1(-)B7-H1(high)F4/80(low) and have morphology of lymphoblasts with active Ig loci but no gene rearrangement. Within weeks of Raptor deletion, the MLICs account for nearly 50% of bone marrow cells and are found throughout both the lymphoid and non-lymphoid organs. Nevertheless, the MLICs are not malignant as they undergo very limited proliferation in vivo. Importantly, the MLICs broadly express pattern-recognition receptors and produce large amounts of inflammatory cytokines in response to all TLR ligands tested, rendering the host highly susceptible to pathogen-associated molecular patterns. Our data suggest that hematopoietic cell-intrinsic mTORC1 prevents development of self-destructive innate immune attack by suppressing generation of MLICs.
ORGANISM(S): Mus musculus
PROVIDER: GSE67863 | GEO | 2017/12/05
SECONDARY ACCESSION(S): PRJNA281089
REPOSITORIES: GEO
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