Original articles
Jing Jin, Nina Xue, Yuan Liu, Rong Fu, Mingjin Wang, Ming Ji, Fangfang Lai, Jinping Hu, Xiaojian Wang, Qiong Xiao, Xiaoying Zhang, Dali Yin, Liping Bai, Xiaoguang Chen, Shuan Rao. A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models[J]. Acta Pharmaceutica Sinica B, 2020, 10(2): 276-288

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models
Jing Jina, Nina Xuea, Yuan Liub, Rong Fua, Mingjin Wanga, Ming Jia, Fangfang Laia, Jinping Hua, Xiaojian Wanga, Qiong Xiaoa, Xiaoying Zhanga, Dali Yina, Liping Baic, Xiaoguang Chena, Shuan Raob
a State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China;
b Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
c State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute, for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P1 modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3+ T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P1 agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.
Key words:    S1P1    S1P1 agonist    IMMH002    Lymphocyte    Psoriasis   
Received: 2019-06-19     Revised: 2019-10-16
DOI: 10.1016/j.apsb.2019.11.006
Funds: This work is supported by the CAMS Innovation Fund for Medical Sciences (2016-I2M-3-008, China), National Natural Science Foundation of China (NSFC Nos. 81872923 and 81473096), Beijing Natural Science Foundation (No. 7172140, China) and The Drug Innovation Major Project (No. 2018ZX09711001-003, China).
Corresponding author: Jing Jin, Xiaoguang Chen, Shuan Rao     Email:rebeccagold@imm.ac.cn;chxg@imm.ac.cn;raoshuan1@smu.edu.cn
Author description:
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Jing Jin
Nina Xue
Yuan Liu
Rong Fu
Mingjin Wang
Ming Ji
Fangfang Lai
Jinping Hu
Xiaojian Wang
Qiong Xiao
Xiaoying Zhang
Dali Yin
Liping Bai
Xiaoguang Chen
Shuan Rao

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