Sabira, Mohammed and Aparna , Jayasekharan S and Manendra Babu , Lankadasari and Harikumar, Kuzhuvelil B (2020) Regulatory role of SphK1 in TLR7/9-dependent type I interferon response and autoimmunity. FASEB journal, 34 (3). pp. 4329-4347. ISSN 1530-6860

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Abstract

Plasmacytoid dendritic cells (pDCs) express Toll like receptors (TLRs) that modulate the immune response by production of type I interferons. Here, we report that sphingosine kinase 1 (SphK1) which produces the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P), plays a critical role in the pDC functions and interferon production. Although dispensable for the pDC development, SphK1 is essential for the pDC activation and production of type I IFN and pro-inflammatory cytokines stimulated by TLR7/9 ligands. SphK1 interacts with TLRs and specific inhibition or deletion of SphK1 in pDCs mitigates uptake of CpG oligonucleotide ligands by TLR9 ligand. In the pristane-induced murine lupus model, pharmacological inhibition of SphK1

Item Type:	Article
Uncontrolled Keywords:	auto-immunity; interferon; plasmacytoid dendritic cells; sphingosine 1-Phosphate; sphingosine kinase; systemic lupus erythematosus.
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	17 Mar 2021 06:54
Last Modified:	17 Mar 2021 06:54
URI:	http://rgcb.sciencecentral.in/id/eprint/1020

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