Collagen type I signaling reduces the expression and the function of human receptor activator of nuclear factor -κB ligand (RANKL) in T lymphocytes

✍ Scribed by Steve Gendron; Julie Couture; Fawzi Aoudjit

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 371 KB
• Volume: 35
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200535065

✦ Synopsis

Abstract

The mechanisms by which β1 integrins modulate T cell functions are still poorly defined. We have previously reported that signaling via the collagen type I (Coll I) receptor, α2β1 integrin, inhibited FasL expression and protected Jurkat T cells from activation‐induced cell death (AICD). In this study, we examined whether Coll I signaling in T cells also modulates the expression of the human receptor activator of nuclear factor‐κB ligand (RANKL), a recently identified TNF family member which has important functions in osteoclastogenesis, cell survival and apoptosis. Our results show that in both Jurkat T cells and human primary T cells, Coll I signaling significantly reduces activation‐induced RANKL expression by 50–60%. We also found that RANKL is not involved in AICD but participates in doxorubicin‐induced apoptosis of leukemia T cell lines including Jurkat, CEM and HSB‐2. In this respect, Coll I protected leukemia T cell lines from doxorubicin‐induced apoptosis by inhibiting doxorubicin‐induced RANKL expression. Together, our results suggest that by limiting the production of RANKL, Coll I signaling may contribute to the resistance of leukemia T cells to chemotherapy. Our study also emphasizes the importance Coll I signaling may have in the control of RANKL‐associated T cell functions.