摘要
It has been documented that TLR7 stimulation triggers not only antiviral responses, but also alleviates experimental asthma. Considering the implication of invariant NKT (iNKT) cells in both situations, we postulated that they might contribute to the anti-inflammatory effect of TLR7 ligands. We show in this study that spleen cells activated by the TLR7 agonist resiquimod (R848) attenuate allergic inflammation upon adoptive transfer when they are recovered from wild-type, but not from iNKT cell-deficient Jalpha18(-/-) mice, which proves the specific involvement of this regulatory population. Furthermore, we provide evidence that IFN-gamma is critical for the protective effect, which is lost when transferred iNKT cells are sorted from IFN-gamma-deficient mice. In support of a direct activation of iNKT cells through TLR7 signaling in vivo, we observed a prompt increase of serum IFN-gamma levels, associated with upregulation of CD69 expression on iNKT cells. Moreover, we demonstrate that iNKT cells effectively express TLR7 and respond to R848 in vitro by producing high levels of IFN-gamma in the presence of IL-12, consistent with the conclusion that their contribution to the alleviation of allergic inflammation upon treatment with TLR7 ligands is mediated through IFN-gamma.
摘要译文
它已被记载，TLR7刺激触发不仅抗病毒反应，而且还减轻了实验性哮喘。考虑不变NKT（的iNKT）细胞在这两种情况下的含义，我们推测，他们可能有助于TLR7配体的消炎作用。我们表明本研究中，通过所述TLR7激动剂瑞喹莫德（R848）活化脾细胞衰减后过继转移变应性炎症当它们被从野生型中回收，但不能从的iNKT细胞缺损Jalpha18（ - / - ）小鼠，这证明了这种调节人口的具体参与。此外，我们提供的证据表明，IFN-γ的是用于保护作用，当转印iNKT细胞从IFN-γ的缺陷型小鼠的排序被丢失关键的。在支持通过TLR7信号传导在体内直接激活iNKT细胞的，我们观察到提示增加血清IFN-γ的水平，与CD69的表达对iNKT细胞上调有关。此外，我们证明，iNKT细胞有效表达TLR7和体外通过生产中的IL-12的存在高水平的IFN-γ的响应R848，与它们对过敏性炎症的减轻处理时与TLR7配体的贡献是通过IFN-γ介导的结论是一致的。
Grela F; Aumeunier A; Bardel E; Van LP; Bourgeois E; Vanoirbeek J; Leite-de-Moraes M; Schneider E; Dy M; Herbelin A; Thieblemont N. The TLR7 agonist R848 alleviates allergic inflammation by targeting invariant NKT cells to produce IFN-gamma.[J]. Journal of Immunology, 2011,186(1): 284-290