| First Author | Zheng J | Year | 2020 |
| Journal | J Autoimmun | Volume | 114 |
| Pages | 102508 | PubMed ID | 32624353 |
| Mgi Jnum | J:314882 | Mgi Id | MGI:6806199 |
| Doi | 10.1016/j.jaut.2020.102508 | Citation | Zheng J, et al. (2020) Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE. J Autoimmun 114:102508 |
| abstractText | 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 MOG35-55 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-1beta production, with the unexpected consequence of increased activation-induced apoptosis of MOG35-55 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. |
