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基于 Pru p 3-表位的舌下免疫治疗在桃过敏治疗的小鼠模型中的应用。

Pru p 3-Epitope-based sublingual immunotherapy in a murine model for the treatment of peach allergy.

机构信息

Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.

Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Sevilla, Spain.

出版信息

Mol Nutr Food Res. 2017 Oct;61(10). doi: 10.1002/mnfr.201700110. Epub 2017 Sep 6.

Abstract

SCOPE

Food-specific immunotherapy (SIT) is a promising treatment for lipid transfer protein (LTP)-syndrome. We propose a novel sublingual-SIT (SLIT) that combines a Pru p 3 T-cell peptide and an oligodeoxyribonucleotide (ODN) with CpG motifs (ODN-CpG) as adjuvants to induce a specific Th1/Treg response.

METHODS AND RESULTS

LTP-peach allergic mice were treated sublingually with a combination of a CpG sequence and mono- or tetravalent systems including a Pru p 3 peptide, D (Prup3) or D (Prup3). Mice were challenged intraperitoneally with Pru p 3 one or three weeks after SLIT and tolerance was assessed. Mice treated with D (Prup3)+CpG were protected from anaphylaxis after Pru p 3 challenge. They showed no change in body temperature, lower levels of Pru p 3-specific IgE and IgG1 antibodies and higher levels of sIgG2a compared to the untreated group. They had fewer IgE and IgG1 secreting cells and more sIgG2a secreting cells. Moreover, a significantly lower number of Pru p 3-specific CD4 T cells and a higher number of Treg cells were found, alongside a Th1 cytokine pattern. These changes were maintained for three weeks after stopping treatment.

CONCLUSION

D Prup3+CpG represents a promising SIT for food allergy. It is easily synthesized and induces protection from anaphylaxis to Pru p 3 that is maintained for at least three weeks.

摘要

范围

食物特异性免疫疗法(SIT)是治疗脂质转移蛋白(LTP)综合征的一种有前途的方法。我们提出了一种新的舌下 SIT(SLIT),它结合了普鲁普 3 T 细胞肽和带有 CpG 基序的寡脱氧核苷酸(ODN)作为佐剂,以诱导特异性 Th1/Treg 反应。

方法和结果

LTP-桃过敏的小鼠通过舌下给予包含 CpG 序列和单价或四价系统的组合进行治疗,该系统包括普鲁普 3 肽、D(Prup3)或 D(Prup3)。在 SLIT 后一周或三周,通过腹腔内 challenged Pru p 3 对小鼠进行挑战,并评估耐受性。用 D(Prup3)+CpG 治疗的小鼠在 Pru p 3 挑战后免受过敏反应。与未治疗组相比,它们的体温没有变化,普鲁普 3 特异性 IgE 和 IgG1 抗体水平较低,sIgG2a 水平较高。它们产生的 IgE 和 IgG1 分泌细胞较少,而 sIgG2a 分泌细胞较多。此外,还发现了明显较少的普鲁普 3 特异性 CD4 T 细胞和更多的 Treg 细胞,同时伴有 Th1 细胞因子模式。这些变化在停止治疗后至少持续三周。

结论

D Prup3+CpG 是一种有前途的食物过敏 SIT。它易于合成,可诱导对普鲁普 3 的过敏反应保护,至少持续三周。

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