Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Int Arch Allergy Immunol. 2011;155(2):129-40. doi: 10.1159/000319826. Epub 2010 Dec 22.
Nuclear factor of activated T cells (NFAT) is required for the differentiation of Th2 responses, so we examined its role in mouse experimental asthma and tested the hypothesis that an NFAT blockade with a decoy against NFAT can prevent asthma progression.
To determine the effects of the NFAT decoy oligodeoxynucleotides (ODNs) on the development of airway inflammation, we designed a novel ribbon-type ODN containing two binding sites for NFAT in a single decoy molecule without an open end, which is more stable than a conventional decoy, and largely preserved its structural integrity in the presence of nucleases.
Ribbon-type NFAT decoy ODNs were transfected into ovalbumin (OVA)-sensitized CD3+ T cells in vitro. OVA-immunized mice received these cells by intraperitoneal injection. Airway hyperreactivity (AHR) was measured and the transfected CD3+ T cells' responses to the airways were characterized.
Development of AHR after OVA challenge was effectively abolished after adoptive transfer of ribbon-type NFAT decoy ODN transfected CD3+ T cells. Transfer of ribbon-type decoy significantly reduced the number of inflammatory cells and the concentrations of IL-4, IL-5 and IL-13, but not IFN-γ, in the bronchoalveolar lavage of the recipient mice.
These results suggest the inhibitory effect of ribbon-type decoy ODNs against NFAT on the induction of bronchial asthma. Adoptively transferred CD3+ T cells, which are transfected with NFAT decoy, may be an effective strategy for the treatment of asthma.
活化 T 细胞核因子（NFAT）是 Th2 反应分化所必需的，因此我们研究了其在小鼠实验性哮喘中的作用，并提出了用 NFAT 诱饵阻断 NFAT 可预防哮喘进展的假说。
为了确定 NFAT 诱饵寡脱氧核苷酸（ODN）对气道炎症发展的影响，我们设计了一种新型带状 ODN，该分子在单个诱饵分子中包含两个 NFAT 结合位点，没有开口，比传统的诱饵更稳定，并且在存在核酸酶的情况下其结构完整性得到了很大的保留。
将带状 NFAT 诱饵 ODN 转染到卵清蛋白（OVA）致敏的 CD3+T 细胞中进行体外实验。OVA 免疫的小鼠通过腹腔注射接受这些细胞。测量气道高反应性（AHR），并对转染的 CD3+T 细胞对气道的反应进行特征描述。
OVA 攻击后 AHR 的发展在接受转染带状 NFAT 诱饵 ODN 的 CD3+T 细胞的过继转移后被有效消除。带状诱饵的转移显著降低了受体小鼠支气管肺泡灌洗液中炎症细胞的数量以及 IL-4、IL-5 和 IL-13 的浓度，但 IFN-γ 的浓度没有降低。
这些结果表明，带状诱饵 ODN 对 NFAT 抑制对支气管哮喘的诱导具有抑制作用。转染 NFAT 诱饵的过继转移 CD3+T 细胞可能是治疗哮喘的有效策略。
