title: Activated NKT cells facilitated functional switch of myeloid-derived suppressor cells at inflammation sites in fulminant hepatitis mice.
abstract: Myeloid-derived suppressor cells (MDSCs) confer immunosuppressive properties, but their roles in fulminant hepatitis have not been well defined. In this study, we systematically examined the distribution of MDSCs in bone marrow (BM), liver and spleen, and their functional and differentiation status in an acute fulminant hepatitis mouse model induced by lipopolysaccharide and D-galactosamine (LPS-GalN). Moreover, the interaction between NKT cells and MDSCs was determined. Our study revealed that BM contained the largest pool of MDSCs during pathogenesis of fulminant hepatitis compared with liver and spleen. MDSCs in liver/spleen expressed higher levels of chemokine receptors such as CCR2, CX3CR1 and CXCR2. At inflamed tissues such as liver or spleen, activated NKT cells induced differentiation of MDSCs through cell-cell interaction, which markedly dampened the immunosuppressive effects and promoted MDSCs to produce pro-inflammatory cytokines and activate inflammatory cells. Our findings thus demonstrated an unexpected pro-inflammatory state for MDSCs, which was mediated by the activated NKT cells that precipitated the differentiation and functional evolution of these MDSCs at sites of inflammation.
authors: Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; Blood center of Zhejiang Province, Hangzhou 310000, China.
authors: Danxiao
authors: D
authors: Wu
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
authors: Yu
authors: Y
authors: Shi
authors: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 31000, China.
authors: Cheng
authors: C
authors: Wang
authors: Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Hanwen
authors: H
authors: Chen
authors: Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Qiaoyun
authors: Q
authors: Liu
authors: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors: Jianhua
authors: J
authors: Liu
authors: Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou 310000, China.
authors: Lihuang
authors: L
authors: Zhang
authors: Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: georgewuer@126.com.
authors: Yihua
authors: Y
authors: Wu
authors: Department of Toxicology, School of public health, Zhejiang University School of Medicine, Hangzhou 310058, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: dxia@zju.edu.cn.
authors: Dajing
authors: D
authors: Xia
mesh_terms: D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D056747:Immunomodulation; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D017114:Liver Failure, Acute / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D019707:Receptors, Chemokine
keywords: Fulminant hepatitis; Myeloid-derived suppressor cell; NKT cells