关键词: Algae Colitis Helminth TGF-β TGM Treg

Mesh : Administration, Oral Animals Chlamydomonas reinhardtii Colitis / chemically induced drug therapy Disease Models, Animal Mice Nematospiroides dubius Recombinant Proteins / administration & dosage T-Lymphocytes, Regulatory Transforming Growth Factor beta / administration & dosage

来  源:   DOI:10.1016/j.jbiotec.2021.08.006   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-β mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.
摘要:
炎症性肠病(IBD)是一组免疫疾病,可以产生与炎症症状相关的慢性疼痛和疲劳。IBD的治疗仍然是一个重要的障碍,目前的治疗方法仅部分有效或具有显著的副作用。提示需要引发不同作用方式和给药策略的新疗法.TGM1是一种TGF-β模拟物,是从肠道蠕虫寄生虫螺旋多回中发现的,被认为是由寄生虫产生的,以抑制肠道炎症反应,帮助逃避宿主免疫,使其成为一种新型抗炎生物治疗剂的理想候选者。在这里,我们利用了可食用绿藻衣藻莱茵衣藻的表达系统,以可以摄取的形式重组产生活性TGM1。Reinhardtii强表达TGM1,并且如通过调节性T细胞诱导所测量的,所得重组蛋白具有生物活性。当口服给小鼠时,藻类表达的TGM1能够改善体重减轻,淋巴结病,和DSS诱导结肠炎小鼠模型的疾病症状,证明了这种生物制剂作为IBD新型治疗方法的潜力。
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