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.

中文翻译：

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新型S1P1调节剂IMMH002可改善多种动物模型中的牛皮癣。

牛皮癣的特征在于角质形成细胞的异常增殖，以及免疫细胞渗透到真皮和表皮中，引起皮肤瘙痒，鳞屑和红斑。对于这种慢性炎症性皮肤病的了解仍不清楚，目前所有可用的治疗方法都有其局限性。在这里，我们表明IMMH002，一种新型的口服活性S1P1调节剂，可使外周致病性淋巴细胞脱敏，使其从次级淋巴器官和胸腺流出信号。使用不同的牛皮癣动物模型，我们证明IMMH002可以显着缓解皮肤损伤，如PASI评分和病理损伤评估所揭示的。从机理上讲，IMMH002通过诱导淋巴细胞的归巢来调节CD3 + T淋巴细胞的重新分布，因此，外周血和皮肤中T淋巴细胞的分配减少，而胸腺中的T淋巴细胞则增加。我们的研究结果表明，新型S1P1激动剂IMMH002具有迅速调节T淋巴细胞分布的非凡能力，代表了牛皮癣治疗的有希望的候选药物。