Pires-Lapa Marco Antonio, Koga Marianna Mainardi, da Silva Ildefonso Alves, Filgueiras Luciano Ribeiro, Jancar Sonia
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Prostaglandins Other Lipid Mediat. 2019 Apr;141:34-39. doi: 10.1016/j.prostaglandins.2019.02.001. Epub 2019 Feb 8.
Dendritic cells (DCs) link innate and adaptive immunity. The microenvironment generated during the innate immunity affects DCs and the type of adaptive immunity generated. Lipid mediators are released early in inflammation and could modify the functional state of DCs. Leukotriene B (LTB) has a wide range of effects on macrophages and in the present study we investigated if it also affects DCs. Murine bone marrow-derived DCs were employed and it was found that stimulation of DCs with LTB4 (10 nM) increased the gene expression of the high affinity receptor BLT-1 but not of BLT-2. It also increased the co-stimulatory molecule CD86 expression but did not affect CD80 and CD40. LTB-stimulated DCs acquired the capacity to present antigen to T lymphocytes, evidenced by antigen-specific proliferation of CD4 lymphocytes in co-cultures of ovalbumin-loaded DCs with DO11.10 splenocytes. LTB-stimulated DCs induced Treg proliferation and increased Th2 cytokine IL-13 in the co-cultures. Expression of transcription factor genes, Gata3 and Foxp3 (Th2 and Treg, respectively) were also found increased. However, the expression of Th1 transcription factor (Tbet) and Th17 (RorγT) were not affected. These results indicate that LTB affects DCs and modulates the type of adaptive immune response.
树突状细胞（DCs）连接天然免疫和适应性免疫。天然免疫过程中产生的微环境会影响DCs以及所产生的适应性免疫的类型。脂质介质在炎症早期释放，可能会改变DCs的功能状态。白三烯B（LTB）对巨噬细胞有广泛影响，在本研究中，我们调查了它是否也影响DCs。我们使用了小鼠骨髓来源的DCs，发现用LTB4（10 nM）刺激DCs会增加高亲和力受体BLT-1的基因表达，但不会增加BLT-2的基因表达。它还增加了共刺激分子CD86的表达，但不影响CD80和CD40。LTB刺激的DCs获得了向T淋巴细胞呈递抗原的能力，卵清蛋白负载的DCs与DO11.10脾细胞共培养时CD4淋巴细胞的抗原特异性增殖证明了这一点。LTB刺激的DCs在共培养中诱导调节性T细胞增殖并增加Th2细胞因子IL-13。还发现转录因子基因Gata3和Foxp3（分别为Th2和调节性T细胞）的表达增加。然而，Th1转录因子（Tbet）和Th17（RorγT）的表达不受影响。这些结果表明，LTB影响DCs并调节适应性免疫反应的类型。
