A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models.

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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A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models.

Author: Jing JIN ¹ ; Nina XUE ¹ ; Yuan LIU ² ; Rong FU ¹ ; Mingjin WANG ¹ ; Ming JI ¹ ; Fangfang LAI ¹ ; Jinping HU ¹ ; Xiaojian WANG ¹ ; Qiong XIAO ¹ ; Xiaoying ZHANG ¹ ; Dali YIN ¹ ; Liping BAI ³ ; Xiaoguang CHEN ¹ ; Shuan RAO ²
Author Information

1. 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.
2. Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
3. 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 China.
Publication Type:Journal Article
Keywords: IMMH002; Lymphocyte; Psoriasis; S1P1; S1P1 agonist
From: Acta Pharmaceutica Sinica B 2020;10(2):276-288
CountryChina
Language:English
Abstract: 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 S1P 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 S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.