Interaction between transmembrane TNF and TNFR1/2 mediates the activation of monocytes by contact with T cells
| Autor: | Ulf Wagner, Sunna Hauschildt, Matthias Pierer, Manuela Rossol, Holm Häntzschel, Undine Meusch, Sylke Kaltenhäuser |
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| Rok vydání: | 2007 |
| Předmět: |
Cell signaling
T cell Injections Subcutaneous T-Lymphocytes Immunology Down-Regulation Cell Communication Monocytes Proinflammatory cytokine Cell Line Tumor medicine Immunology and Allergy Humans Receptors Tumor Necrosis Factor Type II Receptor Antibodies Blocking Cells Cultured Chemistry Tumor Necrosis Factor-alpha Monocyte Cell Membrane Membrane Proteins Transfection Coculture Techniques Cell biology medicine.anatomical_structure Receptors Tumor Necrosis Factor Type I Tumor necrosis factor alpha Signal transduction Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-1767 |
| Popis: | Monocytes and monocytic cells produce proinflammatory cytokines upon direct cell contact with activated T cells. In the autoimmune disease rheumatoid arthritis, the pivotal role of TNF-α implies that the interaction between transmembrane TNF-α (mTNF) and the TNF receptors (TNFR1 and TNFR2) might participate in the T cell contact-dependent activation of monocytes. Accordingly, treatment of rheumatoid arthritis by administration of a TNF-α-blocking Ab was found to significantly decrease TNF-α production by monocytes. Several lines of evidence indicated that signaling through TNFR1/2 and through mTNF (reverse signaling) is involved in TNF-α production by monocytes after T cell contact: 1) blocking mTNF on activated T cells leads to a significant reduction in TNF-α production; 2) down-regulation of TNFR1/2 on monocytes by transfection with small interfering RNA results in diminished TNF-α production; 3) blocking or down-regulating TNFR2 on activated T cells inhibits TNF-α production, indicating that mTNF on the monocyte surface mediates signaling; 4) ligation of mTNF on monocytes by surface TNFR2 transfected into resting T cells induces TNF-α production due to reverse signaling by mTNF; and 5) ligation of mTNF on monocytes by a soluble TNFR2:Ig receptor construct induces TNF-α production due to reverse signaling. In conclusion, we identified mTNF and TNFR1/2 as interaction partners contributing to TNF-α production in monocytes. Both pathways initiated by mTNF-TNFR interaction are likely to be inhibited by treatment with anti-TNF-α Abs. |
| Databáze: | OpenAIRE |
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