Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE. Issue 114 (November 2020)

• Record Type: Journal Article
• Authors: Zheng, Jian; Sariol, Alan; Meyerholz, David; Zhang, Qinran; Abrahante Lloréns, Juan E.; Narumiya, Shuh; Perlman, Stanley
• Is Part Of: Journal of autoimmunity. Issue 114(2020)
• Publication Date: 2020-11
• Subjects: EAE -- Prostaglandin D2 -- PTGDR -- DCs -- IL-1β; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2020.102508
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: 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.