Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China.
Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China.
Int Immunopharmacol. 2023 Nov;124(Pt B):110921. doi: 10.1016/j.intimp.2023.110921. Epub 2023 Sep 17.
Our previous findings show that invariant natural killer T (iNKT)cells can promote immunogenic maturation of lung dendritic cells (LDCs) to enhance Th2 cell responses in asthma. It has been accepted that recognition of glycolipid antigens presented by CD1d molecules by the T cell receptors of iNKT cells leads to iNKT cell activation. Therefore, we examine the immunoregulatory influences of anti-CD1d treatment on Th2 cell response and immunogenic maturation of LDCs and subsequently explored whether these influences were dependent on lung iNKT cells in asthmatic mice. We discoveredthat in wild-type mice sensitized and challenged with house dust mite or ovalbumin (OVA), anti-CD1d treatment inhibited Th2 cell response and immunogenic maturation of LDCs. LDCs from asthmatic mice with anti-CD1d treatment had a markedly decreased influence on Th2 cell responses in vivo and in vitro. Furthermore, anti-CD1d treatment reduced the abundance and activation of lung iNKT cells in asthmatic mice. Moreover, in asthmatic iNKT cell-deficient Jα18 mice, anti-CD1d treatment did not influence Th2 cell responses and immunogenic maturation of LDCs. Meanwhile, the quantity of CD40L iNKT cells in asthmatic mice was significant decreased by anti-CD1d treatment. Finally, the inhibition of anti-CD1d treatment on LDC immunogenic maturation and Th2 cell responses in asthmatic mice was reversed by anti-CD40 treatment. Our data suggest that anti-CD1d treatment can suppress Th2 cell responses through inhibiting immunogenic maturation of LDCs dependent on lung iNKT cells, which couldbe partially related to the downregulation of CD40L expression on lung iNKT cells in asthmatic mice.
我们之前的研究结果表明，不变自然杀伤 T(iNKT)细胞可以促进肺树突状细胞(LDC)的免疫原性成熟，从而增强哮喘中的 Th2 细胞反应。人们已经接受了这样一种观点，即 iNKT 细胞的 T 细胞受体识别由 CD1d 分子呈递的糖脂抗原，导致 iNKT 细胞的激活。因此，我们研究了抗 CD1d 治疗对 Th2 细胞反应和 LDC 免疫原性成熟的免疫调节影响，随后探讨了这些影响是否依赖于哮喘小鼠的肺部 iNKT 细胞。我们发现，在对屋尘螨或卵清蛋白(OVA)致敏和激发的野生型小鼠中，抗 CD1d 治疗抑制了 Th2 细胞反应和 LDC 的免疫原性成熟。用抗 CD1d 治疗的哮喘小鼠的 LDC 对体内和体外 Th2 细胞反应的影响明显降低。此外，抗 CD1d 治疗减少了哮喘小鼠肺部 iNKT 细胞的丰度和激活。此外，在哮喘 iNKT 细胞缺陷型 Jα18 小鼠中，抗 CD1d 治疗并不影响 Th2 细胞反应和 LDC 的免疫原性成熟。同时，抗 CD1d 治疗显著降低哮喘小鼠中 CD40L iNKT 细胞的数量。最后，抗 CD40 治疗逆转了抗 CD1d 治疗对哮喘小鼠 LDC 免疫原性成熟和 Th2 细胞反应的抑制作用。我们的数据表明，抗 CD1d 治疗可以通过抑制依赖肺部 iNKT 细胞的 LDC 免疫原性成熟来抑制 Th2 细胞反应，这可能部分与哮喘小鼠肺部 iNKT 细胞上 CD40L 表达的下调有关。
