Expression of activation-induced, T cell–derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis
✍ Scribed by Sabine Blaschke; Peter Middel; Brigitte G. Dorner; Volker Blaschke; Klaus M. Hummel; Richard A. Kroczek; Kristian Reich; Peter Benoehr; Michael Koziolek; Gerhard A. Müller
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 491 KB
- Volume
- 48
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
To evaluate the possible role of activation‐induced, T cell–derived, and chemokine‐related cytokine (ATAC)/lymphotactin (Lptn) in the pathogenesis of rheumatoid arthritis (RA).
Methods
ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme‐linked immunosorbent assay. Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription–polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real‐time PCR. The phenotype of peripheral blood mononuclear cells (PBMCs) expressing ATAC/Lptn was analyzed by intracellular cytokine staining and flow cytometry.
Results
Levels of ATAC/Lptn were similar in sera and synovial fluids from RA patients (n = 20) and osteoarthritis controls (n = 15). In phorbol myristate acetate/ionomycin–stimulated PBMCs, ATAC/Lptn expression was detected in CD8+ T cells and in a significantly increased proportion of CD4+,CD28− T cells from RA patients as compared with healthy controls. In synovial tissues, ATAC/Lptn was predominantly localized in CD3+ T cells in the sublining layer. Lymphocytes, synovial macrophages, and, unexpectedly, fibroblast‐like synoviocytes (FLS) were identified as major target cells for ATAC/Lptn in RA synovium, as determined by analysis of the ATAC/Lptn receptor XCR1. In vitro, ATAC/Lptn stimulation of FLS resulted in a marked down‐regulation of matrix metalloproteinase 2 production.
Conclusion
These data indicate that in RA synovium, ATAC/Lptn is mainly produced by T cells. Considering its function as a lymphocyte‐specific chemoattractant, ATAC/Lptn might be a key modulator for T cell trafficking in the pathogenesis of RA. In addition, functional studies suggest that ATAC/Lptn may exert additional immunomodulatory effects in RA.