Amelioration of type 1 diabetes by recombinant fructose-1,6-bisphosphate aldolase and cystatin derived from Schistosoma japonicum in a murine model

Parasitol Res. 2020 Jan;119(1):203-214. doi: 10.1007/s00436-019-06511-7. Epub 2019 Dec 16.


Infection with helminth parasites or the administration of their antigens can prevent or attenuate autoimmune diseases. To date, the specific molecules that prime the amelioration are only limited. In this study, recombinant Schistosoma japonicum cystatin (rSjcystatin) and fructose-1,6-bisphosphate aldolase (rSjFBPA) were administered to female NOD mice via intraperitoneal (i.p.) injection to characterize the immunological response by the recombinant proteins. We have shown that the administration of rSjcystatin or rSjFBPA significantly reduced the diabetes incidence and ameliorated the severity of type 1 diabetes mellitus (T1DM). Disease attenuation was associated with suppressed interferon-gamma (IFN-γ) production in autoreactive T cells and with a switch to the production of Th2 cytokines. Following rSjcystatin or rSjFBPA injection, regulatory T cells (Tregs) were remarkably increased, which was accompanied by increased expression of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β). Our study suggests that helminth-derived proteins may be useful in strategies to limit pathology by promoting the Th2 response and upregulating Tregs during the inflammatory tissue-damage process in T1DM.

Keywords: Immunoregulation; Schistosoma japonicum; T1DM; rSjFBPA; rSjcystatin.

MeSH terms

  • Animals
  • Cystatins / administration & dosage*
  • Cystatins / genetics
  • Cystatins / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Disease Models, Animal
  • Female
  • Fructose-Bisphosphate Aldolase / administration & dosage*
  • Fructose-Bisphosphate Aldolase / genetics
  • Fructose-Bisphosphate Aldolase / metabolism
  • Helminth Proteins / administration & dosage*
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / genetics
  • Immunologic Factors / metabolism
  • Mice
  • Mice, Inbred NOD
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Schistosoma japonicum / enzymology*
  • T-Lymphocytes, Regulatory / immunology


  • Cystatins
  • Cytokines
  • Helminth Proteins
  • Immunologic Factors
  • Recombinant Proteins
  • Fructose-Bisphosphate Aldolase