Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE

Jian Zheng, Alan Sariol, David Meyerholz, Qinran Zhang, Juan E. Abrahante Lloréns, Shuh Narumiya, Stanley Perlman

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number102508
JournalJournal of Autoimmunity
Volume114
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
Supported in part by grants from the NIH ( RO1 NS36592 ) and National Multiple Sclerosis Society ( RG 5340-A-7 ).

Keywords

  • DCs
  • EAE
  • IL-1β
  • PTGDR
  • Prostaglandin D2

PubMed: MeSH publication types

  • Journal Article

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