Antigen-Specific Suppression of Inflammatory Arthritis Using Liposomes

Antigen-Specific Suppression of Inflammatory Arthritis Using Liposomes
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DOI:
10.4049/jimmunol.0802972
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发表时间:
2009-03-15
影响因子:
4.4
通讯作者:
Thomas, Ranjeny
Thomas, Ranjeny
中科院分区:
医学2区
文献类型:
--
作者:
Capini, Christelle;Jaturanpinyo, Montree;Thomas, Ranjeny

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现有的类风湿性关节炎和其他自身免疫性疾病的治疗方法不是Ag特异性的,这增加了全身毒性的可能性。我们发现鸡蛋磷脂酰胆碱脂体装载Ag (OVA或甲基化BSA)和亲脂性nf - κ B抑制剂(姜黄素、槲皮素或Bay11-7082)以Ag特异性的方式抑制预先存在的免疫反应。我们将负载脂质体注射到银诱导的小鼠体内或注射到患有银诱导的炎症性关节炎的小鼠体内。脂质体原位靶向APCs,抑制细胞对NF-kappa B的反应性,诱导ag特异性FoxP3(+)调节性T细胞。这种调节机制抑制效应T细胞反应和全面的ag诱导关节炎的临床症状。因此,脂质体可以稳定有效地包裹Ags和nf - κ B抑制剂,并且可以很容易地用于递送Ags和抑制剂,以抑制其他自身免疫性和过敏性疾病。中华免疫学杂志,2009,32(2):556- 565。
Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-kappa B inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells' responsiveness to NF-kappa B and inducing Ag-specific FoxP3(+) regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-kappa B inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases. The Journal of Immunology, 2009, 182: 3556-3565.