Methotrexate activated Tregs via the CD73/AMPK/mTOR pathway

Abstract

Psoriasis is a common skin disease that affects about 2% to 3% of people. The cause is unknown and believed to involve the genes and immune system, and the treatments we use now can control psoriasis but do not cure it. This study, from China, aimed to find out the effect and mechanism (way of working) of a drug called methotrexate on cells called regulatory T cells, which have the power to fight back and calm down the skin, as well as its relationship with the pathway of a chemical in the body called adenosine, which is a target in psoriasis therapy. Regulatory T cells (and effector T cells, which can trigger psoriasis) were isolated from the blood of healthy people and patients with psoriasis. Various laboratory tests were used to examine the effect of methotrexate on the adenosine pathway. The authors found that psoriasis patients have regulatory T cells with decreased function, meaning they do not work so well, and reduced CD73 level, which was the starting section of adenosine pathway. Furthermore, methotrexate could restore the immunosuppressive function of regulatory T cells by affecting part of the adenosine pathway, including increasing CD73 expression and regulating its related signal pathway. In conclusion, the study deepens doctors’ and patients’ understanding of methotrexate in the treatment of psoriasis, and contributes to our understanding of psoriasis.