类风湿关节炎（RA）是致残率较高的以关节破坏为特征的自身免疫性疾病，发病机制和治疗一直是人们探索的重点和难点。多项研究显示调节性T细胞(Treg)的功能受损而非数量的减少是RA发病的重要机制之一。 “老药”α-二氟基鸟氨酸(DFMO) 作为抗肿瘤药物,具有价廉、副作用少等优势，不仅能抑制黑色素瘤生长，还能迅速减轻关节炎炎症性疼痛；申请人海外学习期间研究发现，DFMO在动物实验中能显著增强体外Treg的功能，故推测DFMO可能通过增强Treg功能起到治疗RA的作用。本课题拟在体内体外实验中,通过研究RA患者外周血来源的Treg以及应用胶原诱导性关节炎（CIA）动物模型，阐明以下问题:① DFMO是否能改善RA受损的Treg功能，②其对CIA 是否有治疗效果，③其与TNFi对CIA是否存在协同治疗效应。本课题的实施有望为RA的治疗找到能较快投入市场、安全、有效、低价的“新药”提供科学实验依据。

（限3000 characters）: .Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized by synovial inflammation and destruction of joint cartilage and bone. Despite major advances, the aetiology of this disease is not completely understood and the management of RA remains a big challenge. Safe, effective and affordable strategies to deal with RA are still an urgent priority for health systems. Since the discovery of CD4+CD25+FOXP3+ regulatory T cells (Treg), there has been intense investigation aimed at determining how they protect an organism from autoimmunity. And it has now become clear that Treg have a central role in protecting an individual from RA and defect in the suppressive function of Treg instead of reduced Treg number contributes to the development of this disease.ɑ-difluoromethylornithine (DFMO) is an anti-proliferative agent, inhibiting ornithine decarboxylase (ODC) which is the first enzyme in the polyamine pathway. It has been studied as a therapeutic and chemo-preventive agent for tumour-bearing animals and cancer patients. Previous studies suggested that administration of DFMO could rapidly control inflammatory pain in arthritic animal model. And we have recently found that DFMO could not only inhibit melanoma-the risk of which may be increased by the expensive tumour necrosis factor inhibitors (TNFi)-in vivo, but also boost immunosuppressive function of Treg in vitro. Hence, we hypothesize that DFMO might be a novel treatment for RA. In the present study, we are trying to elucidate: ①whether or not DFMO has the ability to restore suppressive function of Treg induced from peripheral blood mononuclear cell (PBMC) of RA patients; ②whether DFMO has therapeutic effect on collagen-induced arthritis (CIA) mouse model and if the effect is achieved at least part by up-regulating Treg function; ③if the combination of DFMO and TNFi could be used as a therapeutic approach in CIA. Our research might open the door for the rapid translation of these important findings into the clinic and shed new light for the development of a safe, effective and affordable treatment for RA.