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276 Low-dose il-2 circumvented mtor signallingsignaling in t cells in the treatment of sle
  1. J He1,
  2. X Sun1,
  3. J Li1,
  4. R Zhang1,
  5. D Yu2 and
  6. Z Li1
  1. 1Peking Univ. People’s Hospital, Rheumatology and Immunology, Beijing, China
  2. 2School of Biomedical Sciences, ImmunologyClayton, Victoria, Australia

Abstract

Background and aims mTOR signalling is proved to be one of the most important pathway in the pathogenesis in SLE. However, in patients with SLE, whether mTOR pathway can be activated by low-dose IL-2 remained unclear.This study is to clarify the effects of low-dose IL-2 therapy on mTOR signalling in the treatment of SLE.

Methods Eight patients with active SLE were treated with 1 million IU IL-2. Phophrylation of S6 ribosomal protein (S6RP), AKT and pSTAT5 were measured before and after the first 2 week of low-dose rhIL-2 administration. C57BL/6 mice (male, 8–12 weeks old) were intraperitoneally immunised with SRB and followed by administration of different doses (low:10 000 IU and hight:3 00 000 IU) of rhIL-2 or PBS from day 3 to day 9. The ratio of Th1, Th2, Tfh, Th17, Tfh and Treg as well as the level of S6RP, AKT and pSTAT5 were assayed by flow cytometry.

Results Low-dose IL-2 was efficient and well tolerated in active SLE, and was associated with expansion of Treg cells (p<0.001) and reductions of Tfh and Th17 cells (p=<0.001). No significant change of pS6RP and pAKT was observed. On the other hand, there was a signfciant induction of the activation of STAT5. In mouse studies, low-dose IL-2 inhibited the differentiation of Th17 cells and Tfh cells. Comparing with high dose IL-2 group, there was no significantly increased mTOR activity after low-dose IL-2 administration.

Conclusions Low-dose IL-2 might circumvent mTOR pathway and play a regulatory role in the T cells in lupus.

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