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

doi:10.1016/j.jaut.2020.102508

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

Journal article

Open access

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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 and Stanley Perlman

Journal of autoimmunity, Vol.114, pp.102508-102508

11/2020

DOI: 10.1016/j.jaut.2020.102508

PMID: 32624353

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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. •Increased T cell activation occurred in PTGDR−/- mice resulting in T cell apoptosis.•AICD decreased T cell infiltration into, and demyelination in CNS during EAE.•Decreased PGD2/PTGDR signaling in DCs resulted in increased IL-1β expression.•Anakinra treatment in PTGDR−/- mice increased EAE severity.

EAE

Prostaglandin D2

IL-1β

DCs

PTGDR

Details

Title: Subtitle: Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE
Creators: Jian Zheng - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA
Alan Sariol - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA, USA
David Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA, USA
Qinran Zhang - School of Mathematics and Statistics, Wuhan University, Wuhan, PR China
Juan E Abrahante Lloréns - University of Minnesota Informatics Institute (UMII), Minneapolis, MN, USA
Shuh Narumiya - Department of Pharmacology, Kyoto University, Tokyo, 606-8501, Japan
Stanley Perlman - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Journal of autoimmunity, Vol.114, pp.102508-102508
DOI: 10.1016/j.jaut.2020.102508
PMID: 32624353
NLM abbreviation: J Autoimmun
ISSN: 0896-8411
eISSN: 1095-9157
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000002, name: NIH, award: RO1 NS36592; DOI: 10.13039/100000890, name: National Multiple Sclerosis Society, award: RG 5340-A-7
Language: English
Date published: 11/2020
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984070957102771

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