title: Tuning the rheostat of the myelopoietic system via Fas and TRAIL.
abstract: During the last decade, the concerted effort of numerous scientific groups has expanded our understanding of the finely tuned network present within bone marrow for the regulation of the hematopoietic system. This network, comprising humoral and cellular cross talk, is responsible for the adaptation of hematopoietic populations to demands as they arise. Major components of this control system are death receptors and their specific ligands, which eliminate superfluous cells once they have fulfilled their respective functions. The important role of Fas (CD95/Apo-1), one member of this death receptor family, in the regulation of T- and B-cell functions has been established. Alteration of Fas expression and/or function in lymphoid cells may contribute to the development of autoimmunity and/or neoplastic diseases. In addition to controlling lymphoid compartments, Fas is also involved in the regulation of myeloid cell functions. More recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its specific receptors (TRAIL-R) have been identified as further members of this death receptor/ligand family. The TRAIL-R/TRAIL system is of vital importance for the maturation and functioning of immune effector cells of lymphoid, as well as myeloid, origin. In the present review, we have summarized current knowledge about both death receptor/ligand systems in the expansion and functioning of cells from the myeloid compartments, highlighted their role in normal hematopoiesis, and assessed their alterations in pathologic or neoplastic conditions.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, Laboratory of Molecular Cytology, University of Innsbruck Medical School, Anichstrasse 35, Innsbruck, Austria. richard.greil@uibk.ac.at
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Gabriele
authors.initials: G
authors.lastname: Anether
authors.forename: Karin
authors.initials: K
authors.lastname: Johrer
authors.forename: Inge
authors.initials: I
authors.lastname: Tinhofer
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; D058851:GPI-Linked Proteins; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008954:Models, Biological; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor