1. Methotrexate restores the function of peripheral blood Treg cells in psoriasis vulgaris via CD73/AMPK/mTOR pathway
Kexiang Yan1，Wen Xu2,#，Yike Huang1，Zhenghua Zhang1，Qiong Huang1，Ying Ma1，Ling Han1
#Contributed equally to this article
1 Department of Dermatology, Huashan Hospital, Shanghai, China
2 State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, shanghai, , China
British Journal of Dermatology. DOI: /bjd.16560

2. Dr. Ling Han, Lead researcher

3. Introduction What’s already known?
CD73+ Tregs was markedly reduced in psoriasis vulgaris patients compared to healthy individuals. MTX has been widely used to treat psoriasis, and it was reported that MTX could upregulate the expression of CD73 in melanoma.

4. Objective
The molecular mechanism of MTX in treating psoriasis remains partly unknown, which were investigated in this study.

5. Methods
Regulatory T cells (Treg) and effector T cells (Teff cells) were isolated from the blood of healthy people and patients.
The proliferation of Teff cells was detected by CFSE assay.

6. Methods The IFN-γ and IL-17 level were analyzed by Elisa assay.
The expression of CD73 and FoxP3 were determined by Flow cytometric analysis.
The expression of proteins in AMPK/mTOR pathway were detected by Western blots

7. Results
Compared with healthy people, immune suppression function of Treg from psoriasis patient attenuated, and the expression of CD73 in Treg cells reduced.
CD73
CD25
CD73
CD25
Normal Psoriasis

8. Results
MTX could significantly restore immune suppression function of IL-17-secreting Treg cells to inhibit aberrant proliferation of Teff cells in psoriatic patients, and reverse downregulation of CD73, upregulate p-AMPK and inhibit p- mTOR, and downregulate the IL- 17 and IFN-γ level.

9. Discussion
Our study found that, the secretion of IL-17 was elevated and the expression of CD73 was significantly downregulated ，which further confirmed the attenuated function of Treg cells in psoriasis patients.
And AMPK phosphorylation was greatly reduced, the mTOR levels were correspondingly elevated in psoriatic patients.

10. Discussion
MTX could significantly restore the immune suppression function of Treg cells in psoriasis patients, as well as downregulate the IL-17 and IFN-γ level. Moreover, it can also increase CD73 levels, upregulate AMP phosphorylation, and inhibit mTOR phosphorylation.

11. Discussion
These studies might underline the mechanism of how MTX treats psoriasis partly, thus contributing to our understanding of psoriasis therapy

12. Conclusions What does this study add?
We investigated the effect and mechanism of MTX on Treg function as well as its relationship with the CD73/AMPK/mTOR pathways in psoriasis therapy.

13. Research Team

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