Ankylosing Spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation

Wright, P. B., McEntegart, A., McCarey, D., McInnes, I. B. , Siebert, S. and Milling, S. W. F. (2016) Ankylosing Spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation. Rheumatology, 55(1), pp. 120-132. (doi:10.1093/rheumatology/kev245) (PMID:26320138) (PMCID:PMC4676904)

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Abstract

Objective. AS is a systemic inflammatory disease of the SpA family. Polymorphisms at loci including HLA-B27, IL-23R and ERAP-1 directly implicate immune mechanisms in AS pathogenesis. Previously, in an SpA model, we identified HLA-B27–mediated effects on dendritic cells that promoted disease-associated Th17 cells. Here we extend these studies to AS patients using deep immunophenotyping of candidate pathogenic cell populations. The aim of our study was to functionally characterize the immune populations mediating AS pathology. Methods. Using 11-parameter flow cytometry, we characterized the phenotype and functions of lymphocyte and myeloid cells from peripheral blood, and the synovial phenotype of AS patients and age-matched healthy controls. Results. Significantly fewer circulating CD1c-expressing dendritic cells were observed in AS patients, offset by an increase in CD14− CD16+ mononuclear cells. Ex vivo functional analysis revealed that this latter population induced CCR6 expression and promoted secretion of IL-1β and IL-6 when co-cultured with naive CD4+ T cells. Additionally, systemic inflammation in AS patients significantly correlated with increased proportions of activated CCR9+ CD4+ T cells. Conclusion. CD14− CD16+ mononuclear cells may contribute to AS by promoting Th17 responses, and antigen-presenting cells of mucosal origin are likely to contribute to systemic inflammation in AS.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Siebert, Dr Stefan and Milling, Professor Simon and Wright, Miss Pamela and McCarey, Dr David
Authors: Wright, P. B., McEntegart, A., McCarey, D., McInnes, I. B., Siebert, S., and Milling, S. W. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Rheumatology
Publisher:Oxford University Press
ISSN:1462-0324
ISSN (Online):1462-0332
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Rheumatology 55(1):120-032
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580881Dendritic Cells in Ankylosing SpondylitisSimon MillingArthritis Research UK (ARUK)19853III -IMMUNOLOGY