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The therapeutic effect of dendritic cells expressing indoleamine 2,3-dioxygenase (IDO) on an IgA nephropathy mouse model

  • Nephrology - Original Paper
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Abstract

Objective

IgA nephropathy (IgAN) is one of the most common glomerulonephritis in the world, especially in Asian population. IgAN usually progresses slowly, but it is still an important cause of chronic renal failure. IgAN is characterized by abnormal increase of IgA1 level and deposition in mesangium. At present, there is no specific treatment.

Materials and methods

Previous reports have shown that DC cells expressing immunosuppressive factors can significantly reduce the symptoms of arthritis in arthritis models. Indoleamine 2,3-dioxygenase (IDO) is an important tryptophan degrading enzyme and an important factor regulating immunotolerance. DC expressing functional IDO can inhibit effector T cells by consuming essential tryptophan and/or producing toxic metabolites and promoting the differentiation of Treg cells, which exhibits immunosuppressive effect. In this study, we constructed a IgAN mouse model. The mature DC cells overexpressing IDO were induced in vitro and transfused back to IgAN mice to observe their effects on inflammation and renal injury.

Results

The results showed that overexpression of IDO did not affect the maturation of DC cells. The proportion of CD3 + CD4 + and CD3 + CD8 + cells decreased significantly and the proportion of CD4 + CD25 + Foxp3 + cells increased significantly in kidney tissue of IgAN mice after the reinfusion of IDO-expressing DC. The contents of IL-2, IL-4, IL-6, and IL-17A in kidney tissue of IgAN mice also decreased significantly, the damage of kidney tissue was alleviated, ACR was decreased, collagen fibre content in kidney tissue was decreased, and IgA deposition in glomerular mesangium was decreased in IgAN mice.

Conclusions

It has the potential to treat IgAN by upregulating the expression of IDO in DC cells by genetic engineering and reinfusion into vivo.

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Acknowledgements

This study was supported by Hunan key research and development program-key research and development projects in the field of social development (2017SK2143), Changsha Science and technology bureau (kq1701061).

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Authors and Affiliations

  1. Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People’s Hospital, Hunan Normal University, Hunan Clinical Research Center for Chronic Kidney Disease, No. 61 Jiefang West Road, Changsha, 410002, Hunan, P. R. China

    Kanghan Liu, Yiya Yang, Yinyin Chen, Shiyao Li, Yuting Gong & Yumei Liang

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  1. Kanghan Liu
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  2. Yiya Yang
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  3. Yinyin Chen
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Correspondence to Yumei Liang.

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Liu, K., Yang, Y., Chen, Y. et al. The therapeutic effect of dendritic cells expressing indoleamine 2,3-dioxygenase (IDO) on an IgA nephropathy mouse model. Int Urol Nephrol 52, 399–407 (2020). https://doi.org/10.1007/s11255-019-02365-1

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  • DOI: https://doi.org/10.1007/s11255-019-02365-1

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