eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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SCImago Journal & Country Rank
3/2022
vol. 47
 
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abstract:
Experimental immunology

Rapamycin relieves lupus nephritis by regulating TIM-3 and CD4+CD25+Foxp3+ Treg cells in an MRL/lpr mouse model

Yan-fang Gao
1
,
Xiu-zhao Fan
2
,
Rong-shan Li
1, 2
,
Xiao-shuang Zhou
1, 2

1.
Department of Nephrology, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China
2.
Department of Nephrology, Shanxi Provincial People’s Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, China
Cent Eur J Immunol 2022; 47 (3): 206-217
Online publish date: 2022/09/15
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Lupus nephritis (LN) is a severe consequence of systemic lupus erythematosus (SLE) and is an important driver of morbidity and mortality in SLE. Treg cells and TIM-3 play an important role in the pathogenesis of LN. The beneficial effect of rapamycin on LN has been confirmed in both mouse models and patients, but the effect of rapamycin on Treg cells and TIM-3 is not yet completely understood. In this study, rapamycin treatment attenuated proteinuria, histological damage, and renal deposition of C3, and improved renal function. Spleen and renal draining lymph node weight and serum levels of anti-dsDNA antibodies were also improved by rapamycin. Furthermore, the frequency of Treg cells and Treg functional molecules, such as cytotoxic T cell antigen 4 (CTLA-4), interleukin 10 (IL-10), and transforming growth factor β1 (TGF-β1), increased significantly after treatment with rapamycin in MRL/lpr mice. We also found that expression of TIM-3 was significantly decreased in CD4+ T cells and Treg cells in mice treated with rapamycin. In summary, the study demonstrated that rapamycin treatment induced preferential expansion of CD4+CD25+Foxp3+ Tregs with increased expression of CTLA-4, IL-10, and TGF-β1, and decreased TIM-3 expression, thereby ameliorating lupus nephritis in the MRL/lpr mouse model.
keywords:

rapamycin, lupus nephritis, TIM-3, Treg cells, MRL/lpr

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