A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice
Adaptive autoimmunity is restrained by controlling population sizes and pathogenicity of harmful clones, while innate destruction is controlled at effector phase. We report here that deletion of Rptor in mouse hematopoietic stem/progenitor cells causes self-destructive innate immunity by massively i...
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eLife Sciences Publications Ltd
2017-12-01
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| Online Access: | https://elifesciences.org/articles/32497 |
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doaj-2c277510baba41af8018bb2c448ed5dd2021-05-05T13:58:50ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.32497A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in miceFei Tang0https://orcid.org/0000-0003-1475-5028Peng Zhang1https://orcid.org/0000-0002-6218-1885Peiying Ye2Christopher A Lazarski3Qi Wu4Ingrid L Bergin5Timothy P Bender6Michael N Hall7Ya Cui8Liguo Zhang9Taijiao Jiang10Yang Liu11https://orcid.org/0000-0002-9442-700XPan Zheng12https://orcid.org/0000-0003-2598-3544Center for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United States; Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaCenter for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United StatesDepartment of Neurology, University of Michigan Medical School, Ann Arbor, United StatesULAM In-Vivo Animal Core, University of Michigan Medical School, Ann Arbor, United StatesDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, United StatesBiozentrum, University of Basel, Basel, SwitzerlandKey Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaCenter for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United StatesCenter for Cancer and Immunology Research, Children's Research Institute, Children’s National Medical Center, Washington, United StatesAdaptive autoimmunity is restrained by controlling population sizes and pathogenicity of harmful clones, while innate destruction is controlled at effector phase. We report here that deletion of Rptor in mouse hematopoietic stem/progenitor cells causes self-destructive innate immunity by massively increasing the population of previously uncharacterized innate myelolymphoblastoid effector cells (IMLECs). Mouse IMLECs are CD3-B220-NK1.1-Ter119- CD11clow/-CD115-F4/80low/-Gr-1- CD11b+, but surprisingly express high levels of PD-L1. Although they morphologically resemble lymphocytes and actively produce transcripts from Immunoglobulin loci, IMLECs have non-rearranged Ig loci, are phenotypically distinguishable from all known lymphocytes, and have a gene signature that bridges lymphoid and myeloid leukocytes. Rptor deletion unleashes differentiation of IMLECs from common myeloid progenitor cells by reducing expression of Myb. Importantly, IMLECs broadly overexpress pattern-recognition receptors and their expansion causes systemic inflammation in response to Toll-like receptor ligands in mice. Our data unveil a novel leukocyte population and an unrecognized role of Raptor/mTORC1 in innate immune tolerance.https://elifesciences.org/articles/32497hemotopoiesisTSC-mTOR signalingmTORC1innate immunityinflammationimmune tolerance |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Fei Tang Peng Zhang Peiying Ye Christopher A Lazarski Qi Wu Ingrid L Bergin Timothy P Bender Michael N Hall Ya Cui Liguo Zhang Taijiao Jiang Yang Liu Pan Zheng |
| spellingShingle |
Fei Tang Peng Zhang Peiying Ye Christopher A Lazarski Qi Wu Ingrid L Bergin Timothy P Bender Michael N Hall Ya Cui Liguo Zhang Taijiao Jiang Yang Liu Pan Zheng A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice eLife hemotopoiesis TSC-mTOR signaling mTORC1 innate immunity inflammation immune tolerance |
| author_facet |
Fei Tang Peng Zhang Peiying Ye Christopher A Lazarski Qi Wu Ingrid L Bergin Timothy P Bender Michael N Hall Ya Cui Liguo Zhang Taijiao Jiang Yang Liu Pan Zheng |
| author_sort |
Fei Tang |
| title |
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice |
| title_short |
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice |
| title_full |
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice |
| title_fullStr |
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice |
| title_full_unstemmed |
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice |
| title_sort |
population of innate myelolymphoblastoid effector cell expanded by inactivation of mtor complex 1 in mice |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2017-12-01 |
| description |
Adaptive autoimmunity is restrained by controlling population sizes and pathogenicity of harmful clones, while innate destruction is controlled at effector phase. We report here that deletion of Rptor in mouse hematopoietic stem/progenitor cells causes self-destructive innate immunity by massively increasing the population of previously uncharacterized innate myelolymphoblastoid effector cells (IMLECs). Mouse IMLECs are CD3-B220-NK1.1-Ter119- CD11clow/-CD115-F4/80low/-Gr-1- CD11b+, but surprisingly express high levels of PD-L1. Although they morphologically resemble lymphocytes and actively produce transcripts from Immunoglobulin loci, IMLECs have non-rearranged Ig loci, are phenotypically distinguishable from all known lymphocytes, and have a gene signature that bridges lymphoid and myeloid leukocytes. Rptor deletion unleashes differentiation of IMLECs from common myeloid progenitor cells by reducing expression of Myb. Importantly, IMLECs broadly overexpress pattern-recognition receptors and their expansion causes systemic inflammation in response to Toll-like receptor ligands in mice. Our data unveil a novel leukocyte population and an unrecognized role of Raptor/mTORC1 in innate immune tolerance. |
| topic |
hemotopoiesis TSC-mTOR signaling mTORC1 innate immunity inflammation immune tolerance |
| url |
https://elifesciences.org/articles/32497 |
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