Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice
Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice
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DOI：
10.4049/jimmunol.1102628
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发表时间：
2012-05-01
影响因子：
4.4
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Li, Li-Ping;Fang, Yi-Chuan;Saito, Shigeru
本研究旨在确定不变NKT（iNKT）细胞是否在炎症诱导的早产中发挥重要作用。在腹膜内注射LPS的野生型（WT）C57 BL/6小鼠和iNKT细胞缺陷型J α 18（-/-）小鼠中测定早产和胎儿死亡率。通过流式细胞术分析蜕膜免疫细胞的百分比，包括活化的亚群和共刺激分子的表达。用ELISA法检测蜕膜单个核细胞培养上清中Th 1和Th 2细胞因子的产生。在某种程度上，J α 18（-/-）小鼠对LPS诱导的早产具有抗性。J α 18（-/-）小鼠中蜕膜CD 3（+）和CD 49 b（+）细胞的比例略低于WT J α 18（+/+）小鼠，而J α 18-null小鼠中几乎没有发现CD 3（+）CD 49 b（+）细胞。LPS处理的J α 18（-/-）小鼠中活化的蜕膜DC、T细胞和NK细胞的百分比显著低于WT小鼠。J α 18（-/-）小鼠蜕膜CD 11 c（+）细胞上的CD 40、CD 80和CD 86表达水平也显著低于WT小鼠。LPS处理的J α 18（-/-）小鼠蜕膜单核细胞培养上清中Th 1细胞因子IFN-γ和IL-12 p70的平均浓度明显低于LPS诱导的WT小鼠。此外，与对照PBS组和注射LPS但正常分娩的小鼠相比，WT和null小鼠中LPS诱导的早产小鼠中活化的CD 11 c（+）细胞、CD 3（+）细胞和CD 49 b（+）细胞的比例显著更高。我们的研究结果表明，iNKT细胞可能在炎症诱导的早产中发挥重要作用。免疫学杂志，2012，188：4681-4689。
This study sought to determine whether invariant NKT (iNKT) cells play an essential role in inflammation-induced preterm delivery. Preterm delivery and fetal death rates were determined in wild-type (WT) C57BL/6 mice and iNKT cell-deficient J alpha 18(-/-) mice injected i.p. with LPS. The percentages of decidual immune cells, including activated subsets, and costimulatory molecule expression were analyzed by flow cytometry. Th1 and Th2 cytokine production in the culture supernatants of decidual mononuclear cells was measured by ELISA. To some extent, J alpha 18(-/-) mice were resistant to LPS-induced preterm delivery. The proportions of decidual CD3(+) and CD49b(+) cells were slightly lower in J alpha 18(-/-) mice than in WT J alpha 18(+/+) mice, whereas almost no CD3(+)CD49b(+) cells could be found in J alpha 18-null mice. The percentages of activated decidual DCs, T cells, and NK cells were significantly lower in LPS-treated J alpha 18(-/-) mice than in WT mice. The CD40, CD80, and CD86 expression levels on decidual CD11c(+) cells from J alpha 18(-/-) mice were also significantly lower than in WT mice. Mean concentrations of Th1 cytokines IFN-gamma and IL-12p70 in the culture supernatants of decidual mononuclear cells from LPS-treated J alpha 18(-/-) mice were apparently lower than those of LPS-induced WT mice. Additionally, the proportions of activated CD11c(+) cells, CD3(+) cells, and CD49b(+) cells in LPS-induced preterm delivery mice were strikingly higher in both WT and null mice when compared with the control PBS group and LPS-injected but normally delivered mice. Our results suggest that iNKT cells may play an essential role in inflammation-induced preterm birth. The Journal of Immunology, 2012, 188: 4681-4689.