Priming of autoreactive T cells in lymph nodes by dendritic cells (DCs) is critical for the pathogenesis of experimental autoimmune encephalitis (EAE). DC activation reflects a balance of pro- and anti-inflammatory signals. One anti-inflammatory factor is prostaglandin D2 signaling through its cognate receptor, D-prostanoid receptor 1 (PTGDR), on myeloid cells. Loss of PTGDR signaling might be expected to enhance DC activation and EAE but here we show that PTGDR^−/− mice developed only mild signs of MOG_35-55 peptide immunization-induced EAE. Compared to wild type mice, PTGDR^−/− mice exhibited less demyelination, decreased leukocyte infiltration and diminished microglia activation. These effects resulted from increased pro-inflammatory responses in the lymph nodes, most notably in IL-1β production, with the unexpected consequence of increased activation-induced apoptosis of MOG_35-55 peptide-specific T cells. Conditional deletion of PTGDR on DCs, and not other myeloid cells ameliorated EAE. Together, these results demonstrate the indispensable role that PGD₂/PTGDR signaling on DCs has in development of pathogenic T cells in autoimmune demyelination.

树突状细胞 (DC) 启动淋巴结中的自身反应性 T 细胞对于实验性自身免疫性脑炎 (EAE) 的发病机制至关重要。DC 激活反映了促炎和抗炎信号的平衡。一种抗炎因子是前列腺素 D2 信号通过其在骨髓细胞上的同源受体 D-前列腺素受体 1 (PTGDR)。预计 PTGDR 信号的丧失可能会增强 DC 激活和 EAE，但在这里我们表明 PTGDR ^{-/ -}小鼠仅出现 MOG _35-55肽免疫诱导的 EAE 的轻微迹象。与野生型小鼠相比，PTGDR ^{-/ -}小鼠表现出较少的脱髓鞘、减少的白细胞浸润和减少的小胶质细胞活化。这些效应是由于淋巴结中促炎反应的增加，最显着的是 IL-1β 的产生，其意外后果是 MOG _35-55肽特异性 T 细胞的活化诱导凋亡增加。DCs 上 PTGDR 的条件性删除，而不是其他骨髓细胞改善 EAE。总之，这些结果证明了DC 上的PGD ₂ /PTGDR 信号传导在自身免疫性脱髓鞘中致病性 T 细胞的发育中具有不可或缺的作用。