PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis

Midgley, Angela; Barakat, Dina; Braitch, Manjit; Nichols, Calen; Nebozhyn, Mihailo; Edwards, Laura J.; Fox, Susan C.; Gran, Bruno; Robins, R. Adrian; Showe, Louise C.; Constantinescu, Cris S.

Abstract

© 2020 Elsevier GmbH IL-23 is a potent stimulus for Th17 cells. These cells have a distinct developmental pathway from Th1 cells induced by IL-12 and are implicated in autoimmune and inflammatory disorders including multiple sclerosis (MS). TGF-β, IL-6, and IL-1, the transcriptional regulator RORγt (RORC) and IL-23 are implicated in Th17 development and maintenance. In human polyclonally activated T cells, IL-23 enhances IL-17 production. The aims of our study were: 1). To validate microarray results showing preferential expression of platelet activating factor receptor (PAF-R) on IL-23 stimulated T cells. 2). To determine whether PAF-R on activated T cells is functional, whether it is co-regulated with Th17-associated molecules, and whether it is implicated in Th17 function. 3). To determine PAF-R expression in MS. We show that PAF-R is expressed on activated T cells, and is inducible by IL-23 and IL-17, which in turn are induced by PAF binding to PAF-R. PAF-R is co-expressed with IL-17 and regulated similarly with Th17 markers IL-17A, IL-17F, IL-22 and RORC. PAF-R is upregulated on PBMC and T cells of MS patients, and levels correlate with IL-17 and with MS disability scores. Our results show that PAF-R on T cells is associated with the Th17 phenotype and function. Clinical Implications Targeting PAF-R may interfere with Th17 function and offer therapeutic intervention in Th17-associated conditions, including MS.

Citation

Midgley, A., Barakat, D., Braitch, M., Nichols, C., Nebozhyn, M., Edwards, L. J., …Constantinescu, C. S. (2021). PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis. Immunobiology, 226(1), Article 152023. https://doi.org/10.1016/j.imbio.2020.152023

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2020
• Online Publication Date: Dec 3, 2020
• Publication Date: Jan 1, 2021
• Deposit Date: Dec 10, 2020
• Publicly Available Date: Dec 4, 2021
• Journal: Immunobiology
• Print ISSN: 0171-2985
• Electronic ISSN: 1878-3279
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 226
• Issue: 1
• Article Number: 152023
• DOI: https://doi.org/10.1016/j.imbio.2020.152023
• Keywords: Immunology; Immunology and Allergy; Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/5131153
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0171298520305453
• Additional Information: This article is maintained by: Elsevier; Article Title: PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis; Journal Title: Immunobiology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.imbio.2020.152023; Content Type: article; Copyright: © 2020 Elsevier GmbH. All rights reserved.