Enrichment of circulating IL-17-secreting IL-23 receptor-positive gamma-delta T cells in patients with active ankylosing spondylitis

Kenna, Tony J., Davidson, Stuart I., Duan, Ran, Bradbury, Linda A., McFarlane, Janelle, Smith, Malcolm, Weedon, Helen, Street, Shayna, Thomas, Ranjeny, Thomas, Gethin P. and Brown, Matthew A. (2012) Enrichment of circulating IL-17-secreting IL-23 receptor-positive gamma-delta T cells in patients with active ankylosing spondylitis. Arthritis and Rheumatism, 64 5: 1420-1429. doi:10.1002/art.33507

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Author Kenna, Tony J.
Davidson, Stuart I.
Duan, Ran
Bradbury, Linda A.
McFarlane, Janelle
Smith, Malcolm
Weedon, Helen
Street, Shayna
Thomas, Ranjeny
Thomas, Gethin P.
Brown, Matthew A.
Title Enrichment of circulating IL-17-secreting IL-23 receptor-positive gamma-delta T cells in patients with active ankylosing spondylitis
Formatted title
Enrichment of circulating IL-17-secreting IL-23 receptor-positive γδ T cells in patients with active ankylosing spondylitis
Journal name Arthritis and Rheumatism   Check publisher's open access policy
ISSN 0004-3591
1529-0131
0893-7524
Publication date 2012-05-01
Year available 2012
Sub-type Article (original research)
DOI 10.1002/art.33507
Open Access Status DOI
Volume 64
Issue 5
Start page 1420
End page 1429
Total pages 9
Place of publication Hoboken, NJ, U.S.A.
Publisher John Wiley & Sons
Language eng
Subject 2723 Immunology and Allergy
2745 Rheumatology
2403 Immunology
2736 Pharmacology (medical)
Abstract Objective Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis. Methods The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared. Results The proportion of IL-23Rexpressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23Rpositive ?/d T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on ?/d T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23Rnegative ?/d T cells in AS patients. Furthermore, ?/d T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28. Conclusion Recently, mouse models have shown IL-17secreting ?/d T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17producing cells, increased IL-23R expression may regulate the function of this putative pathogenic ?/d T cell population.
Formatted abstract
Objective: Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS, but the role IL-23-signalling plays in disease pathogenesis is unclear.

Methods: To investigate this further, we examined IL-23R expression in AS, rheumatoid arthritis (RA), psoriatic arthritis (PsA) patients and healthy controls (HC).

Results: The proportion of T cells expressing IL-23R in the periphery of AS patients was twofold higher than in controls, specifically driven by a 3-fold increase in IL-23R+ γδ T cells in AS patients; IL-17+ CD4+ and CD8+ cells were unchanged. This increased IL-23R expression on γδ T cells was also associated with enhanced IL-17 secretion, with no IL-17 production seen from IL-23R- γδ T cells in AS patients. Furthermore, γδ T cells from AS patients were heavily skewed towards IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28.

Conclusions: Recently, mouse models have shown IL-17 secreting γδ T cells to be pathogenic in infection and autoimmunity. Our data is the first description of a potentially pathogenic role for these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17 producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γδ T cell population.
Keyword Collagen-induced arthritis
Ror-gamma-T
Cutting edge
IL-23 receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 569830
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 20 Mar 2012, 21:44:37 EST by Kylie Hengst on behalf of UQ Diamantina Institute