Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways.
Thymic myoid cells correspond to a muscle-like cell population present in the thymic medulla. They are well conserved throughout species evolution, but their biological role is not known. We demonstrated that myoid cells protected thymocytes from apoptosis as evidenced by a strong decrease of annexin-V-FITC positive thymocytes. This effect was (1) specific of myoid cells compared to thymic epithelial cells; (2) dependent on direct cell-to-cell contacts and (3) triggered rapidly after 2 h in cocultures. This protective phenomenon was due to the activation of prosurvival mechanisms. Indeed, myoid cells activated extracellular-regulated kinases (ERK1/2) and Akt in thymocytes. Myoid cells also influenced thymocyte maturation. We observed an increase in CD4(+) and a decrease in CD8(+) single positive (SP) thymocytes when cocultured with myoid cells, independently of a CD8(+)SP increased death or a CD4(+)SP overproliferation. Consequently, thymic myoid cells protect thymocytes from apoptosis and could also modulate their differentiation process.
Le Panse
R
R
CNRS UMR 8078, IPSC, Université Paris XI, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. rozen.lepanse@ccml.u-psud.fr
Berrih-Aknin
S
S
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D004789:Enzyme Activation; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
D017304:Annexin A5; D005456:Fluorescent Dyes; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016650:Fluorescein-5-isothiocyanate