Midgley, Angela, Barakat, Dina, Braitch, Manjit, Nichols, Calen, Nebozhyn, Mihailo, Edwards, Laura J, Fox, Susan C, Gran, Bruno, Robins, R Adrian, Showe, Louise C et al (show 1 more authors)
(2021)
PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis.
Immunobiology, 226 (1).
152023-.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-Lymphocytes, Cells, Cultured, Humans, Multiple Sclerosis, Platelet Activating Factor, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled, Interleukin-17, Tissue Array Analysis, Lymphocyte Activation, Adult, Middle Aged, Female, Male, Interleukin-23, Th17 Cells |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Sep 2021 08:32 |
| Last Modified: | 18 Jan 2023 23:01 |
| DOI: | 10.1016/j.imbio.2020.152023 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3115161 |
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