Collagen type I signaling reduces the expression and the function of human receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes.
The mechanisms by which beta1 integrins modulate T cell functions are still poorly defined. We have previously reported that signaling via the collagen type I (Coll I) receptor, alpha2beta1 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-kappaB 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.
Gendron
Steve
S
Centre de Recherche en Rhumatologie/Immunologie CHUQ, Pavillon CHUL, Faculté de Médecine, Université Laval, Québec, Canada.
Couture
Julie
J
Aoudjit
Fawzi
F
D017209:Apoptosis / Q000276:immunology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; D024042:Collagen Type I; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human