Synthetic polymer as an adjuvant in collagen-induced arthritis.

Synthetic polymer as an adjuvant in collagen-induced arthritis.
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DOI:
10.1002/9780470942390.mo130226
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发表时间:
2014-03-21
影响因子:
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通讯作者:
Nandakumar, Kutty Selva
Nandakumar, Kutty Selva
中科院分区:
其他
文献类型:
--
作者:
Shakya, Akhilesh Kumar;Nandakumar, Kutty Selva

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胶原诱导性关节炎(CIA)是经典的实验性关节炎动物模型,与人类类风湿性关节炎有许多相似之处。然而,最广泛使用的诱导CIA的方法利用弗氏佐剂,其可使引发的免疫应答偏斜并且还造成毒性问题。该单位描述了一种新的方法,诱导CIA使用定义明确的刺激响应性合成聚合物,聚N-异丙基丙烯酰胺为基础的佐剂,与关节软骨蛋白胶原II型(CII)混合。作为佐剂的PNiPAAm是可生物降解的和生物相容的,并且不偏斜免疫应答。因此,它有助于开发关节炎模型,用于以无偏倚的方式研究抗原和组织特异性自身免疫应答。该模型对于分析疾病途径、确定关节炎调控基因的位置、验证现有疗法以及探索新的治疗靶点具有重要价值。此外,这种新开发的PNiPAAm佐剂允许在独立于toll样受体的几种自身免疫性疾病中使用特异性自身抗原研究疾病诱导,以及优化用于感染性疾病的疫苗递送系统。
Collagen-induced arthritis (CIA), the classical animal model for experimental arthritis, resembles human rheumatoid arthritis in several aspects. However, the most widely used method of inducing CIA utilizes Freund's adjuvants, which can skew the elicited immune responses and also pose toxicity problems. This unit describes a new method of inducing CIA using a well defined stimuli-responsive synthetic polymer, poly-N-isopropylacrylamide-based adjuvant, mixed with the joint cartilage protein collagen type II (CII). PNiPAAm as an adjuvant is biodegradable and biocompatible, and does not skew immune responses. Thus, it is helpful in the development of arthritis models for studying antigen and tissue -specific autoimmune responses in an unbiased manner. This model is valuable for analyzing disease pathways, positional identification of genes regulating arthritis, validation of existing therapies, and exploring new therapeutic targets. Furthermore, this newly developed PNiPAAm adjuvant allows investigation of disease induction using specific autoantigens in several autoimmune diseases independently of toll-like receptors, as well as optimization of vaccine delivery systems for infectious diseases.