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

  • Immunology and Host-Parasite Interactions - Original Paper
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Abstract

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.

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Abbreviations

rSjcystatin:

recombinant Schistosoma japonicum cystatin

rSjFBPA:

recombinant Schisotosoma japonicum fructose-1,6-bisphosphate aldolase

T1DM:

type 1 diabetes mellitus

CY:

cyclophosphamide

NOD:

nonobese diabetic

Tregs:

regulatory T cells

ELISA:

enzyme-linked immunosorbent assay

SEA:

soluble egg antigen

SWA:

soluble worm antigen

IBD:

inflammatory bowel disease

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Acknowledgments

We thank Dr. Li He at Wuhan University School of Medicine for providing rSjcystatin plasmid.

Funding

The work was funded by the Natural Science Foundation of Anhui Province (No 1308085MH124) and the Natural Science Research of Educational Department Anhui Province (No. KJ2015ZD31).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280 Mohe Road, Shanghai, 201999, China

    Ke Yan, Bo Wang & Zhengrong Zhong

  2. Department of Comprehensive Treatment II, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 800 Xiangyin Road, Shanghai, 200433, China

    Huabang Zhou

  3. Department of Pathogen Biology, Provincial Laboratories of Pathogen Biology and Zoonoses Anhui, Anhui Medical University, No. 81 Meishan Road, Hefei, 230022, China

    Qingli Luo & Jilong Shen

  4. Department of Second Dental Clinic, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280 Mohe Road, Shanghai, 201999, China

    Yunxia Xu

  5. Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Roda, Bengbu, 233004, China

    Zhengrong Zhong

Authors
  1. Ke Yan
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  2. Bo Wang
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  3. Huabang Zhou
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  4. Qingli Luo
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  5. Jilong Shen
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  7. Zhengrong Zhong
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Contributions

KY and XYX were responsible for all experiments and drafted the manuscript. BW, HBZ, and QLL helped in the analysis and interpretation of tests. ZRZ and JLS were responsible for design of the study and reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Yunxia Xu or Zhengrong Zhong.

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Ethics approval and consent to participate

This study was approved by the Animal Ethics Committee of Bengbu Medical College. And the consent to participate is not applicable.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Section Editor: Xing-Quan Zhu

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Key findings

Administration of rSjcystatin or rSjFBPA could reduce the incidence and ameliorated the severity of T1DM. Disease attenuation was associated with suppressed IFN-γ production and a shift of Th1 to Th2. And Tregs were remarkably increased, which was accompanied by increased expression of IL-10 and TGF-β.

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Yan, K., Wang, B., Zhou, H. et al. Amelioration of type 1 diabetes by recombinant fructose-1,6-bisphosphate aldolase and cystatin derived from Schistosoma japonicum in a murine model. Parasitol Res 119, 203–214 (2020). https://doi.org/10.1007/s00436-019-06511-7

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  • DOI: https://doi.org/10.1007/s00436-019-06511-7

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