Comparison of blood and synovial fluid th17 and novel peptidase inhibitor 16 Treg cell subsets in juvenile idiopathic arthritis.
OBJECTIVE
Early recognition and treatment of juvenile idiopathic arthritis (JIA) can prevent joint damage and minimize side effects of medication. The balance between proinflammatory and antiinflammatory mechanisms is known to be important in JIA, and we therefore investigated T cell subsets including Th cells, autoaggressive Th17 cells, and regulatory T cells (Treg), including a novel Treg subset in peripheral blood (PB) and synovial fluid (SF) of patients with JIA.


METHODS
Fifty children with JIA were enrolled in our study. Frequency, phenotype, and function of T lymphocytes in PB and SF were characterized using flow cytometry. Migration capabilities of PB and SF cells were compared.


RESULTS
Synovial T cells showed different phenotype and function compared with PB T cells, with an increased proportion of memory T cells, expression of CCR4, CCR5, CXCR3, interleukin 23R, and an increased ratio of Th17 to Treg. Although Treg were increased in SF compared with the PB, we found a significant decrease in the numbers of peptidase inhibitor 16 (PI16)+ Treg in active joints compared with peripheral blood. Coexpression of CCR4 and CCR6 was reduced on PI16+ Treg in PB and SF of patients with JIA compared with healthy children, however the ability of these cells to migrate toward their ligands was unaffected.


CONCLUSIONS
This is a comprehensive characterization of novel PI16+ Treg and Th17 cells in matched blood and synovial fluid samples of patients with JIA. Despite an increased number of Treg within the inflamed joint, lower numbers of PI16+ Treg but high numbers of Th17 cells might contribute to the inability to control disease.
Women's and Children's Health Research Institute (WCHRI), North Adelaide, and the Discipline of Paediatrics, University of Adelaide, Adelaide, Australia.
Randall H
RH
Grose
Deborah J
DJ
Millard
Chris
C
Mavrangelos
Simon C
SC
Barry
Heddy
H
Zola
Ian C
IC
Nicholson
Weng Tarng
WT
Cham
Christina A
CA
Boros
Doreen
D
Krumbiegel
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; C501293:PI16 protein, human