Title |
IFN-γ–STAT1–iNOS Induces Myeloid Progenitors to Acquire Immunosuppressive Activity
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Published in |
Frontiers in immunology, September 2017
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DOI | 10.3389/fimmu.2017.01192 |
Pubmed ID | |
Authors |
Shu-Han Yang, Liang Li, Yu-Qing Xie, Yuan Yao, Cai-Yue Gao, Liang-Huan Liao, Hong-Di Ma, M. Eric Gershwin, Zhe-Xiong Lian |
Abstract |
Autoimmune diseases often induce dysregulated hematopoiesis with altered number and function of hematopoietic stem and progenitor cells (HSPCs). However, there are limited studies on the direct regulation of HSPCs on T cells, which are often detrimental to autoimmunity. Here, we found that in a murine model of Concanavalin A-induced autoimmune hepatitis, LSK (Lineage(-)Sca-1(+)c-Kit(+))-like cells accumulated in liver, spleen, and bone marrow (BM), which were myeloid progenitors (Lineage(-)Sca-1(-)c-Kit(+)) that upregulated Sca-1 expression upon T cell-derived IFN-γ stimulation. Strikingly, BM LSK-like cells from mice induced by Con A to develop autoimmune hepatitis or alternatively myeloid progenitors from wild-type mice possessed strong in vitro suppressive ability. Their suppressive function depended on T cell-derived IFN-γ in a paracrine fashion, which induced STAT1 phosphorylation, inducible nitric oxide synthase expression, and nitric oxide production. Blocking IFN-γ/IFN-γ receptor interaction, knockout of STAT1, or iNOS inhibition abrogated their suppressive function. In addition, the suppressive function was independent of differentiation; mitomycin C-treated myeloid progenitors maintained T cell suppressive ability in vitro. Our data demonstrate a mechanism of inflammation induced suppressive function of myeloid progenitors, which may participate directly in suppressing T cell-mediated immunopathology. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 2 | 11% |
Student > Master | 2 | 11% |
Student > Postgraduate | 2 | 11% |
Researcher | 2 | 11% |
Student > Ph. D. Student | 2 | 11% |
Other | 3 | 16% |
Unknown | 6 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 5 | 26% |
Agricultural and Biological Sciences | 3 | 16% |
Immunology and Microbiology | 3 | 16% |
Medicine and Dentistry | 1 | 5% |
Unknown | 7 | 37% |