Some studies have shown that maturation of dendritic cells (DCs) is modulated directly by pathogen components via pattern recognition receptors such as Toll-like receptors, but also by signal like CD40 ligand (CD40 L or CD154) mediated by activated T cells. Several reports indicate that invariant natural killer T (iNKT) cells up-regulate CD40 L upon stimulation and thereby induce activation and maturation of DCs through crosslink with CD40. Our previous findings indicated that iNKT cells promote Th2 cell responses through the induction of immunogenic maturation of lung DCs (LDCs) in the asthmatic murine, but its mechanism remains unclear. Therefore, we investigated the immunomodulatory effects of blockade of CD40 L using anti-CD40 L treatment on Th2 cell responses and immunogenic maturation of LDCs, and further analyzed whether these influences of blockade of CD40 L were related to lung iNKT cells using iNKT cell-deficient mice and the combination treatment of specific iNKT cell activation with anti-CD40 L treatment in murine models of asthma. Our findings showed that blockade of CD40 L using anti-CD40 L treatment attenuated Th2 cell responses in wild-type (WT) mice, but not in CD1d-deficient mice sensitized and challenged with ovalbumin (OVA) or house dust mite (HDM). Meanwhile, blockade of CD40 L down-regulated immunogenic maturation of LDCs in WT mice, but not in CD1d-deficient mice sensitized and challenged with OVA. Additionally, agonistic anti-CD40 treatment reversed the inhibitory effects of anti-CD40 L treatment on Th2 cell responses and LDC activation in an OVA-induced mouse model of asthma. Furthermore, LDCs from asthmatic mice treated with anti-CD40 L could significantly reduce the influence on Th2 cell responses in vivo and in vitro. Finally, α-Galactosylceramide plus anti-CD40 L treatment stimulated lung iNKT cells, but suppressed Th2 cell responses in the asthmatic mice. Taken together, our data raise an evidence that blockade of CD40 L attenuates Th2 cell responses through the inhibition of immunogenic maturation of LDCs, which may be at least partially related to lung iNKT cells in murine models of asthma.

中文翻译：

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CD40L的阻滞抑制肺树突状细胞的免疫原性成熟：对哮喘小鼠的肺iNKT细胞的作用有影响。

一些研究表明，病原体成分​​通过模式识别受体（例如Toll样受体）直接调节树突状细胞（DC）的成熟，但也可以通过活化T细胞介导的信号（如CD40配体（CD40 L或CD154））进行调节。几篇报道表明，不变的自然杀伤T细胞（iNKT）在刺激后会上调CD40 L，从而通过与CD40交联来诱导DC的激活和成熟。我们以前的发现表明，iNKT细胞通过诱导哮喘鼠肺DC（LDC）的免疫原性成熟来促进Th2细胞应答，但其机制尚不清楚。因此，我们研究了使用抗CD40 L处理阻断CD40 L对Th2细胞反应和最不发达国家免疫原性成熟的免疫调节作用，并进一步分析了在哮喘小鼠模型中，使用iNKT细胞缺陷小鼠阻断CD40 L的这些影响是否与肺iNKT细胞有关，以及特异性iNKT细胞激活与抗CD40 L治疗的联合治疗。我们的发现表明，在野生型（WT）小鼠中使用抗CD40 L处理对CD40 L的阻断作用减弱了Th2细胞的反应，但在用卵清蛋白（OVA）或屋尘螨（HDM）致敏和攻击的CD1d缺陷小鼠中却没有。同时，在野生型小鼠中，CD40 L的阻断下调了LDCs的免疫原性成熟，但在OVA致敏和攻击的CD1d缺陷型小鼠中却没有。此外，在OVA诱发的哮喘小鼠模型中，抗CD40激动剂治疗可以逆转抗CD40 L治疗对Th2细胞反应和LDC活化的抑制作用。此外，用抗CD40 L治疗的哮喘小鼠的LDC可以在体内和体外显着降低对Th2细胞反应的影响。最后，α-半乳糖苷神经酰胺加抗CD40 L处理可刺激哮喘小鼠的肺iNKT细胞，但抑制Th2细胞反应。综上所述，我们的数据提出了一个证据，即CD40 L的阻断通过抑制LDCs的免疫原性成熟而减弱Th2细胞应答，LDCs可能至少部分与哮喘小鼠模型中的肺iNKT细胞有关。