Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4+ T lymphocytes in rheumatoid arthritis.
The massive infiltration of synovium with CD4+ T cells during the course of rheumatoid arthritis (RA) implies the expression of chemoattractant factors by resident synovial cells. Therefore, we analyzed the expression of IL-16, a potent chemoattractant for CD4+ T cells, to account for the accumulation of CD4+ T cells in RA. Indeed, IL-16 was found to be significantly elevated in synovial fluid (SF) from patients with RA as compared to non-RA arthritis (p < 0.001), osteoarthritis (p < 0.001) and controls (p < 0.001). Chemotaxis studies showed IL-16 to contribute to the strong chemotactic activities of RA-SF. In situ hybridization (ISH) revealed IL-16 mRNA-expressing cells located within the lining layer of rheumatoid synovial tissue. In the sublining area, only scattered IL-16 transcript-positive cells could be detected, mainly adjacent to blood vessels. By a double-labeling technique, combining ISH for IL-16 mRNA and immunohistochemistry for CD68, synovial fibroblast-like, CD68-negative cells were identified as a major source of IL-16 mRNA within RA synovium. This study demonstrates that synovial fibroblasts produce IL-16 in RA and thus mediate chemoattraction of CD4+ cells into synovial tissue.
Franz
J K
JK
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital, Zürich, Switzerland.
Kolb
S A
SA
Hummel
K M
KM
Lahrtz
F
F
Neidhart
M
M
Aicher
W K
WK
Pap
T
T
Gay
R E
RE
Fontana
A
A
Gay
S
S
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002630:Chemotactic Factors / Q000276:immunology* / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D019410:Interleukin-16 / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology
D002630:Chemotactic Factors; D019410:Interleukin-16