S1PR4 Signaling Attenuates ILT 7 Internalization To Limit IFN-α Production by Human Plasmacytoid Dendritic Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Christina DillmannAndreas Weigert

Abstract

Plasmacytoid dendritic cells (pDCs) produce large amounts of type I IFN in response to TLR7/9 ligands. This conveys antiviral effects, activates other immune cells (NK cells, conventional DCs, B, and T cells), and causes the induction and expansion of a strong inflammatory response. pDCs are key players in various type I IFN-driven autoimmune diseases such as systemic lupus erythematosus or psoriasis, but pDCs are also involved in (anti-)tumor immunity. The sphingolipid sphingosine-1-phosphate (S1P) signals through five G-protein-coupled receptors (S1PR1-5) to regulate, among other activities, immune cell migration and activation. The present study shows that S1P stimulation of human, primary pDCs substantially decreases IFN-α production after TLR7/9 activation with different types of CpG oligodeoxynucleotides or tick-borne encephalitis vaccine, which occurred in an S1PR4-dependent manner. Mechanistically, S1PR4 activation preserves the surface expression of the human pDC-specific inhibitory receptor Ig-like transcript 7. We provide novel information that Ig-like transcript 7 is rapidly internalized upon receptor-mediated endocytosis of TLR7/9 ligands to allow high IFN-α production. This is antagonized by S1PR4 signaling, thus ...Continue Reading

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Citations

Mar 3, 2018·Cellular Microbiology·Arielle M Bryan, Maurizio Del Poeta
Jan 10, 2018·Immunology·Matthew Collin, Venetia Bigley
Apr 26, 2018·International Journal of Molecular Sciences·Joseph M KulinskiAna Olivera
Aug 9, 2019·Neuropsychopharmacology Reports·Yui MurataKazuya Iwamoto
Jan 24, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabira MohammedKuzhuvelil B Harikumar
Jul 15, 2020·The Journal of Clinical Investigation·Catherine OleschAndreas Weigert
Aug 6, 2019·Frontiers in Immunology·Andreas WeigertBernhard Brüne
Mar 30, 2017·Clinical Science·Marc WeidenbuschHans-Joachim Anders
Dec 11, 2021·Cellular and Molecular Gastroenterology and Hepatology·Chung Hwan HongEun Hee Koh

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