Tenascin-C inhibits β1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1 – 5 repeats to fibronectin

Abstract

The extracellular matrix consists of different proteins interacting to form a meshwork-like structure. T lymphocyte adhesion to individual matrix proteins is mainly regulated at the adhesion receptor level, but it is conceivable that the composition of the matrix itself may affect T lymphocyte adhesion to individual proteins. We have addressed the latter point by studying the effect of the matrix protein tenascin-C (TN-C) on T lymphocyte adhesion to fibronectin. Here we report that TN-C inhibits adhesion of T lymphocytes and MOLT-4 lymphoma cells to fibronectin. We demonstrate that a TN-C fragment consisting of fibronectin type III repeats 1-5 (TNfnIII 1-5) but not TNfnIII A-D and TNfnIII 6-8 inhibited alpha5beta1 and alpha4beta1 integrin-mediated T lymphocyte and MOLT-4 adhesion to fibronectin. At concentrations that did not inhibit adhesion, TNfnIII 1-5 still prevented MOLT-4 cells from spreading on fibronectin. Preincubation and co-immobilization of TNfnIII 1-5 with fibronectin was more effective in inhibiting MOLT-4 adhesion to fibronectin than soluble TNfnIII 1-5 present during the adhesion test. Using an enzyme-linked immunosorbent assay we could demonstrate binding of TNfnIII 1-5 to fibronectin and fibronectin fragments. Taken together, these data demonstrate that the TNfnIII 1-5 domain is implicated in the inhibition of T lymphocyte adhesion to fibronectin caused by TN-C, and indicate that this effect involves the binding of TN-C repeats TNfnIII 1-5 to fibronectin.

Tenascin-C in Chronic Canine Hepatitis: Immunohistochemical Localization and Correlation with Necro-Inflammatory Activity, Fibrotic Stage, and Expression of Alpha-Smooth Muscle Actin, Cytokeratin 7, and CD3+ Cells

“…This has also been reported in tumors. 31 Two mutually enhancing factors may play a role: TN-C can suppress CD3-mediated T-cell activation, [22][23][24]34,41 while activated CD3+ T-lymphocytes induce plasminogen-dependent proteolysis of TN-C by secreting u-PA. 20 Both may have a negative impact on the progression of fibrosis.…”

Tenascin-C blocks cell-cycle progression of anchorage-dependent fibroblasts on fibronectin through inhibition of syndecan-4

“…As mentioned above, tenascin-C interferes with cell adhesion on fibronectin (Chiquet-Ehrismann et al, 1988;Hauzenberger et al, 1999;Huang et al, 2001). To test whether tenascin-C modulates cell adhesion and proliferation of normal fibroblasts in a fibronectin context, we plated cells on a mixed substratum of fibronectin and tenascin-C. Phalloidin staining revealed that cell spreading was markedly disturbed in REF52 cells 1 h after plating on the mixed substratum ( Figure Figure 2b).…”

Extracellular Matrix of Glioblastoma Inhibits Polarization and Transmigration of T Cells: The Role of Tenascin-C in Immune Suppression

“…Recently, tenascin-C was identified as a prognostic marker for tumor recurrence and shown to play a role in glioblastoma growth and invasion (29). Tenascin-C inhibits b1-integrin-dependent T lymphocyte adhesion to fibronectin (34) and thus potentially inhibits the transmigration processes of Jurkat cells across glioblastoma cells. This speculation is supported by the finding that suppression of tenascin-C in glioma cells using the shRNA technique enhanced the transmigration rate of Jurkat cells and CD3/CD28-activated T cells in our transwell assay.…”