Monocyte derived interleukin (IL)-23 is an important determinant of synovial IL-17A expression in rheumatoid arthritis.
OBJECTIVE
To demonstrate gene expression of interleukin (IL)-17A, IL-23, and IL-12 and to determine the proximity of IL-17A and IL-23 producing cells in rheumatoid synovial tissue.


METHODS
Total RNA was isolated from 25 synovial membranes obtained from 20 patients with rheumatoid arthritis (RA). Quantitative real-time polymerase chain reaction was used to measure IL-17A, IL-12p35, IL-23p19, p40, and GAPDH expression. Immunohistochemistry was utilized to determine cell type and proximity of IL-17A, IL-12, and IL-23 in rheumatoid synovium.


RESULTS
IL-17A was present in 13/25 synovia. IL-12p35 was present in all samples while IL-23p19 was present in 23/25. p40 was present in 23/25 samples. Of the 2 p40- samples both were IL-23p19 and IL-12p35 positive. Mean expression of IL-23p19 was significantly higher in the IL-17A+ versus IL-17A- synovia (0.10 +/- 0.02 ng vs 0.05 +/- 0.01 ng; p < 0.05). There was no difference in IL-12p35 expression between IL-17A+ and IL-17A- synovia (0.5 +/- 0.21 ng vs 0.38 +/- 0.24 ng; p = 0.2). All IL-17A+ cells were in the vicinity of IL-23+ cells. IL-12+ cells were both close to and removed from IL-17A+ cells. Only a proportion of CD3+T cells appeared to produce IL-17A.


CONCLUSIONS
IL-17A gene expression occurs in only a subset of rheumatoid synovial membranes. IL-23 gene expression is higher in IL-17A+ versus IL-17A- membranes. In keeping with this, IL-17A+ and IL-23+ cells colocalize in synovial membranes. IL-17 is not an absolute requirement in RA but may be important in amplifying the inflammatory response. Anti-IL23 therapies may have a role in those patients with IL-17A expression.
Stamp
Lisa K
LK
Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. lisa.stamp@cdhb.govt.nz
Easson
Andrea
A
Pettersson
Linda
L
Highton
John
J
Hessian
Paul A
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology*
D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19