title: Oral administration of recombinant Lactococcus lactis expressing HSP65 and tandemly repeated P277 reduces the incidence of type I diabetes in non-obese diabetic mice.
abstract: Diabetes mellitus type 1 (DM1) is an autoimmune disease that gradually destroys insulin-producing beta-cells. We have previously reported that mucosal administration of fusion protein of HSP65 with tandem repeats of P277 (HSP65-6P277) can reduce the onset of DM1 in non-obese diabetic (NOD) mice. To deliver large amounts of the fusion protein and to enhance long-term immune tolerance effects, in the present study, we investigated the efficacy of using orally administrated L. lactis expressing HSP65-6P277 to reduce the incidence of DM1 in NOD mice. L. lactis strain NZ9000 was engineered to express HSP65-6P277 either constitutively or by nisin induction. After immunization via gavage with the recombinant L. lactis strains to groups of 4-week old female NOD mice for 36 weeks, we observed that oral administration of recombinant L. Lactis resulted in the prevention of hyperglycemia, improved glucose tolerance and reduced insulitis. Immunologic analysis showed that treatment with recombinant L. lactis induced HSP65- and P277- specific T cell immuno-tolerance, as well as antigen-specific proliferation of splenocytes. The results revealed that the DM1-preventing function was in part caused by a reduction in the pro-inflammatory cytokine IFN-γ and an increase in the anti-inflammatory cytokine IL-10. Orally administered recombinant L. lactis delivering HSP65-6P277 may be an effective therapeutic approach in preventing DM1.
authors.affiliation: Forensic Center, Nanjing Forest Police College, Nanjing, People's Republic of China; Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hou
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Rongyue
authors.initials: R
authors.lastname: Cao
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Taiming
authors.initials: T
authors.lastname: Li
authors.affiliation: Minigene Pharmacy Laboratory, School of life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018834:Chaperonin 60 / Q000235:genetics / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D013294:Lactococcus lactis / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000235:genetics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D018834:Chaperonin 60; D016207:Cytokines; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C095402:peptide 277, heat shock protein 60