Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Activation-induced killer cell immunoglobulin-like receptor 3DL2 binding to HLA-B27 licenses pathogenic T cell differentiation in spondyloarthritis

Ridley, Anna, Hatano, Hiroko, Wong-Baeza, Isabel, Shaw, Jacqueline, Matthews, Katherine K., Al-Mossawi, Hussein, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Bowness, Paul and Kollnberger, Simon 2016. Activation-induced killer cell immunoglobulin-like receptor 3DL2 binding to HLA-B27 licenses pathogenic T cell differentiation in spondyloarthritis. Arthritis and Rheumatology 68 (4) , pp. 901-914. 10.1002/art.39515

[thumbnail of Ridley_et_al-2016-Arthritis_&_Rheumatology.pdf] PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB)

Abstract

Objective In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA–B27 and the phenotype and function of KIR-3DL2–expressing CD4+ T cells in SpA. Methods In total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27− and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template-switch anchored reverse transcription–polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme-linked immunosorbent assay. Results Cellular activation induced KIR-3DL2 expression on both naive and effector CD4+ T cells. KIR-3DL2 binding to B27+ cells promoted expression of KIR-3DL2, the Th17-specific transcription factor retinoic acid receptor–related orphan nuclear receptor γt, and the antiapoptotic factor B cell lymphoma 2. KIR-3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen-presenting cells, KIR-3DL2+CD4+ T cells produced less interleukin-2 (IL-2) but more IL-17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR-3DL2 to B27 heavy chains. Conclusion KIR-3DL2 binding to HLA–B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA–B27–KIR-3DL2 interactions for the treatment of B27+ patients with SpA.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: Wiley: 12 months
ISSN: 2326-5191
Date of First Compliant Deposit: 15 June 2016
Date of Acceptance: 12 November 2015
Last Modified: 07 May 2023 06:16
URI: https://orca.cardiff.ac.uk/id/eprint/91848

Citation Data

Cited 39 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics