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. 2019 Sep 4;20(1):32.
doi: 10.1186/s12865-019-0305-0.

Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients

Chunmiao Zhao  1 , Yanfang Chu  1 , Zhaoyun Liang  1 , Bingying Zhang  1 , Xuxia Wang  1 , Xiaona Jing  1 , Meihua Hao  1 , Yiqi Wang  1 , Jia An  1 , Xingzhe Zhang  2 , Liguang Sun  3 , Junwei Chen  4
Affiliations

Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients

Chunmiao Zhao et al. BMC Immunol. .

Abstract

Background: The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients.

Result: Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased.

Conclusion: Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage.

Trial registration: ChiCTR-IPR-16009451 Registration date: 2016/10/16.

Keywords: IL-2; Rapamycin; Systemic lupus erythematosus; Th17 cells; Treg cells.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
FACS analysis of Th17 cells and Treg cells in the PBMCs of refractory SLE patients and healthy controls. a Representative flow cytometric analysis of human Th17 cells (CD4 + IL-17+) isolated from healthy control and SLE patients; b Representative flow cytometric analysis of human Treg cells (CD4 + CD25 + Foxp3+) isolated from healthy control and SLEpatients; c The absolute number of Th17 cells and Treg cells; The ratio of Th17 cells /Treg cells. NSLE = 50; NHC = 70
Fig. 2
Fig. 2
Effect of low-dose IL-2 combined with rapamycin on the populations of Th17 and Treg cells: a The number of Th17 cells; b The absolute number of Treg cells; c The ratio of Th17/Treg One-way analysis of variance (ANOVA) test was performed, and the pairwise comparison was conducted using the LSD test. NSLE = 50
Fig. 3
Fig. 3
Effect of low-dose IL-2 combined with rapamycin on disease parameters in patients with refractory SLE: a The SLEDAI score analysis; b The ESR analysis One-way analysis of variance (ANOVA) test was performed, and the pairwise comparison was conducted using the LSD test. NSLE = 50
Fig. 4
Fig. 4
Effect of low-dose IL-2 combined with rapamycin on drug dose in patients with refractory SLE. a The change of prednison dosage at 0, 6th,12th and 24th week. Prednison; b the HCQ change at different week post treatment; c the MMF change at different week post treatment. One-way analysis of variance (ANOVA) test was performed, and the pairwise comparison was conducted using the LSD test. NSLE = 50
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