Abstract
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-1β 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.
Original language | English (US) |
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Article number | 102508 |
Journal | Journal of Autoimmunity |
Volume | 114 |
DOIs | |
State | Published - Nov 2020 |
Bibliographical note
Publisher Copyright:© 2020 Elsevier Ltd
Keywords
- DCs
- EAE
- IL-1β
- PTGDR
- Prostaglandin D2