Tsinghua University Institute of Immunity Dong Chen's group published a document on "Immunity" to reveal a new mechanism of psoriasis
Release date: 2018-04-13
Psoriasis is a clinical autoimmune skin disease that affects 1% to 2% of the world's population and is currently not fully cured. Patients with psoriasis usually present with abnormal skin: redness, itching, scaling, etc., and are accompanied by certain complications, which seriously affect the quality of life of patients.
Although interleukin-17A (IL-17A) produced in lymphocytes has been shown to play an important role in psoriasis, the initiation and chronic inflammatory mechanisms of this disease are not well understood. Interleukin 25 (IL-25) is another IL-17 family factor that has been found in laboratories including the Dongchen group to regulate allergic reactions and type 2 immune diseases. In the present study, IL-25 was found to be highly expressed in the skin of patients with psoriasis and in a mouse model of psoriasis, and was specifically regulated by IL-17A.
To explore the role of IL-25 in the pathogenesis of psoriasis, the researchers attempted to directly inject IL-25 into the skin of mice and found that direct injection of this cytokine induced a phenotype similar to psoriasis skin inflammation. The researchers then used IL-25 knockout mice to induce a psoriasis mouse model and found psoriasis-like skin inflammation in IL-25 full-knockout and conditional knockout of psoriasis mice. There is a significant drop in the model. Further in vitro experiments have demonstrated that IL-25 stimulation of keratinocytes can directly promote its proliferation and cause high expression of various inflammatory cytokines and chemokines, including its own mRNA expression, thereby further promoting the proliferation of keratinocytes and cells. The cycle changes and this effect is achieved by phosphorylation activation of STAT3.
Mechanism studies have found that IL-25 stimulates tyrosine phosphorylation of its receptor, thereby recruiting and directly activating STAT3 to produce downstream responses. Therefore, this study demonstrates an autocrine mechanism cycle in the skin mediated by IL-25 during the pathogenesis of psoriasis, providing a new perspective for explaining the mechanism of psoriasis and blocking this cycle. The pathway is likely to be a new strategy for the treatment of psoriasis.
Professor Dong Chen of the medical school is the author of this article. Xu Miao, a doctoral student at the School of Life Science of Tsinghua University, is the first author of the paper. Other collaborators of the paper include Tsinghua University, East China Normal University, and the Tenth Affiliated Hospital of Tongji University. Researcher. The research was funded by the Ministry of Science and Technology and the National Natural Science Foundation of China.
Original link:
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Source: Tsinghua Immunity
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