TWEAK promotes the production of Interleukin-17 in rheumatoid arthritis.

Abstract

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that modulates several biological responses by inducing chemokines and proinflammatory cytokines. We hypothesized that TWEAK could promote secretion of IL-17, an amplifier of inflammatory arthritis. To test this, we investigated the capacity of TWEAK to induce IL-17 production in T cells via the fibroblast growth factor-inducible gene 14 (Fn14, also known as TWEAK receptor) signal pathway in rheumatoid arthritis (RA). Fn14 and IL-17 were highly expressed in arthritic tissues of collagen-induced arthritis (CIA) mice. TWEAK induced production of IL-17 alone and synergistically with lipopolysaccharide. In naïve murine T cells, TWEAK promoted Th17 differentiation. The expression of Fn14 was predominant in Th17 cells. TWEAK and IL-17 concentrations were significantly higher in synovial fluid and serum in RA patients than OA patients. In addition, we identified CD4(+)IL-17(+)Fn14(+) cells in synovium from RA patients. TWEAK promoted IL-17 production synergistically with IL-23 or IL-21 and blockade of Fn14 with Fn14-Fc suppressed Th17 differentiation. Conversely, this treatment enhanced Treg differentiation. These results suggest that TWEAK induces IL-17 production and may be a therapeutic target in the treatment of RA.

• Authors: Jin-Sil Park, Mi-Kyung Park, Seon-Yeong Lee, Hye-Jwa Oh, Mi-Ae Lim, Woo-Tae Cho, Eun-Kyung Kim, Ji-Hyeon Ju, Young-Woo Park, Sung-Hwan Park, Mi-La Cho, Ho-Youn Kim
• Journal: Cytokine (Cytokine) Vol. 60 Issue 1 Pg. 143-9 (Oct 2012) ISSN: 1096-0023 [Electronic] England
• PMID: 22819243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Cytokine TWEAK
• Interleukin-17
• Interleukin-23
• Interleukins
• Lipopolysaccharides
• Receptors, Tumor Necrosis Factor
• Recombinant Proteins
• TNFRSF12A protein, human
• TNFSF12 protein, human
• TWEAK Receptor
• Tnfrsf12a protein, mouse
• Tumor Necrosis Factors
• interleukin-21

Topics

• Animals
• Arthritis, Experimental (genetics, metabolism)
• Arthritis, Rheumatoid (blood, genetics, metabolism)
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Cells, Cultured
• Cytokine TWEAK
• Drug Synergism
• Enzyme-Linked Immunosorbent Assay
• Gene Expression (drug effects)
• Interleukin-17 (blood, genetics, metabolism)
• Interleukin-23 (pharmacology)
• Interleukins (pharmacology)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred DBA
• Osteoarthritis (blood, genetics, metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• Recombinant Proteins (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Spleen (cytology, metabolism)
• TWEAK Receptor
• Tumor Necrosis Factors (blood, genetics, pharmacology)