On Dec.29，the Proceedings of the National Academy of Sciences (PNAS) published online the latest research result from Professor Linrong Lu’s group "Phosphatase PP2A is essential for TH17 differentiation". The study revealed the essential role of phosphatase PP2A in regulating TH17 cell differentiation and the development of related autoimmune diseases.
Clinical analysis showed that the expression level of phosphatase PP2A was positively correlated with the severity of disease and IL17A expression in patients with systemic lupus erythematosus, suggesting the involvement of PP2A in the regulation of TH17 differentiation and related inflammatory responses. By using a gene knockout that leads to T cell-specific deletion, Prof. Lu and his colleagues revealed the essential role of Ser/Thr phosphatase PP2A in T_H17 differentiation. They also showed that this works through the regulation of SMAD2/3 phosphorylation status, which elucidates molecular pathways by which PP2A modulates the expression of T_H17 phenotypes. This finding extends our understanding of the close relationship between PP2A overexpression and inflammatory disease. PP2A is a Ser/Thr phosphatase shown to be capable of controlling T_H17 differentiation via modulating R-SMADs activity. This work also demonstrated the translational potential of these findings by showing a therapeutic effect of PP2A inhibitors in controlling autoimmune disease in the encephalomyelitis model.

Ph.D. students Qin Xu and Xuexiao Jin from the Institute of Immunology are the first authors of this study. Other co-authors include Zheng Mingzhu, Deepak Rohila, Fu Guotong, Wen Zhuoyu, and Qi Jun. This is a collaborative research with Professor Wu Songquan from Lishui Medical College, Professor Richard Sloan from Zhejiang University-Edinburgh University, Professor Lie Wang from the Institute of Immunology,Professor Hu Hu from the Department of Pathology and Pathophysiology and Professor Xiang Gao from the Model anima research center in Nanjing University. The corresponding authors of this article is Professor Linrong Lu and Professor Xiang Gao. This study was supported by the National Natural Science Foundation.

Link of the paper：https://www.pnas.org/content/early/2018/12/27/1807484116

Lab link：https://person.zju.edu.cn/llr

Figure 1：PP2A promotes T_H17 cell differentiation through differential regulation of SMAD2 and SMAD3 Phosphorylation ( Adapted from Gustavo J. Martinez, JEM 2017）.