title: Heat Shock Protein 60 in Eggs Specifically Induces Tregs and Reduces Liver Immunopathology in Mice with Schistosomiasis Japonica.
abstract: BACKGROUND
  Parasitic helminths need to suppress the host immune system to establish chronic infections. Paradoxically, immunosuppression induced by the worm also benefits the host by limiting excessive inflammation and tissue damage, which remains the major cause leading to serious morbidity and mortality. Regulatory T cells (Tregs) are key immune regulators of this mutualism. The successive rise in Tregs during schistosome infection plays a critical role in immunoregulation. We and others previously showed that Schistosoma japonicum (S. japonicum) egg antigens (SEA) induce Tregs both in vitro and in vivo. In addition, we identified that SjHSP60 derived from SEA significantly induces Tregs in vivo and in vitro. However, the contribution of SjHSP60 in SEA to Treg induction and the related mechanisms of the Treg induction have not yet been identified.
  
  
  RESULTS
  In this study, we showed that S. japonicum stress protein HSP60 (SjHSP60) was constitutively and extensively expressed in eggs of S. japonicum. SjHSP60 specially induced Tregs in vivo and in vitro without inducing other CD4+ T sub-populations including Th1, Th2 and Th17 cells. Furthermore, we showed that the SjHSP60-depleted SEA almost lost the ability in vitro and displayed a significant impaired ability to induce Tregs in vivo. Finally, our study illustrated that the mechanisms of SjHSP60-mediated induction of Tregs are through both conversion of CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs and expansion of preexisting CD4+CD25+Foxp3+ Tregs in a TLR4-dependent manner.
  
  
  CONCLUSIONS
  Collectively, our findings identify SjHSP60 as a major parasitic contributor of Treg induction in S. japonicum egg antigens, which not only contributes to the better understanding of the mechanism of immunoregulation during helminth infection, but also suggests its potential as a therapeutic target for control of immunopathology, allergic and autoimmune diseases.
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Microbial Engineering, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pathology, Department of Microbiology and Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Su
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D057131:Immune Evasion / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000276:immunology*; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins