title: Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy.
abstract: The roles that thymus cytokines might play in regulating thymic atrophy are not known. Reversing thymic atrophy is important for immune reconstitution in adults. We have studied cytokine mRNA steady-state levels in 45 normal human (aged 3 days to 78 years) and 34 myasthenia gravis thymuses (aged 4 to 75 years) during aging, and correlated cytokine mRNA levels with thymic signal joint (sj) TCR delta excision circle (TREC) levels, a molecular marker for active thymopoiesis. LIF, oncostatin M (OSM), IL-6, M-CSF, and stem cell factor (SCF) mRNA were elevated in normal and myasthenia gravis-aged thymuses, and correlated with decreased levels of thymopoiesis, as determined by either decreased keratin-positive thymic epithelial space or decreased thymic sjTRECs. IL-7 is a key cytokine required during the early stages of thymocyte development. Interestingly, IL-7 mRNA expression did not fall with aging in either normal or myasthenia gravis thymuses. In vivo administration of LIF, OSM, IL-6, or SCF, but not M-CSF, i.p. to mice over 3 days induced thymic atrophy with loss of CD4+, CD8+ cortical thymocytes. Taken together, these data suggest a role for thymic cytokines in the process of thymic atrophy.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: L P
authors.initials: LP
authors.lastname: Hale
authors.forename: J S
authors.initials: JS
authors.lastname: Sundy
authors.forename: J M
authors.initials: JM
authors.lastname: Massey
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
authors.forename: D C
authors.initials: DC
authors.lastname: Douek
authors.forename: D D
authors.initials: DD
authors.lastname: Patel
authors.forename: B F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001284:Atrophy; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D053683:Oncostatin M; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D019089:Stem Cell Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D013950:Thymus Gland / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D053683:Oncostatin M; D016173:Macrophage Colony-Stimulating Factor