A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice
Abstract
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.
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Funding
National Institute of Allergy and Infectious Diseases (AI64350)
- Yang Liu
- Pan Zheng
National Cancer Institute (CA183030)
- Yang Liu
National Institute on Aging (AG036690)
- Pan Zheng
National Cancer Institute (CA171972)
- Yang Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal careand use committee (IACUC) protocols (312-13-12 and #00030574) of the Children's National Medical Center. Every effort was made to minimize suffering.
Reviewing Editor
- Satyajit Rath, Agharkar Research Institute (ARI) and Indian Institute of Science Education and Research (IISER), India
Publication history
- Received: October 3, 2017
- Accepted: December 2, 2017
- Accepted Manuscript published: December 5, 2017 (version 1)
- Version of Record published: January 10, 2018 (version 2)
Copyright
© 2017, Tang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice
eLife 6:e32497.
https://doi.org/10.7554/eLife.32497
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