Getting back at nature: understanding thymic development and overcoming its atrophy.
T cell development is a complex and tightly regulated process involving reciprocal interactions between the thymic stroma and differentiating thymocytes. Normal thymic function is critical for immunity and microenvironmental defects predispose to dysregulation in the T cell compartment. Thymic structure and function are also severely damaged by chemotherapy and pre-transplant conditioning. Furthermore, poor immune competence with ageing is closely linked to thymic atrophy. Overcoming such thymic defects would have immediate application in many diseases, especially the recovery of cancer patients from cytotoxic treatment. Reversing the thymus ageing process via inhibition of atrophic factors such as sex steroids or administration of thymopoietic growth factors is one possible approach. Moreover, it is becoming clear a common thymic epithelial progenitor exists, raising the possibility for de novo thymus generation using emerging stem cell and tissue engineering technologies. Achievement of this goal will open up many avenues for the application of thymus-based immune rejuvenation and manipulation.
Heng
Tracy S P
TS
Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, VIC 3800, Australia.
Chidgey
Ann P
AP
Boyd
Richard L
RL
D000375:Aging / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D001284:Atrophy / Q000139:chemically induced; D004847:Epithelial Cells; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000037:antagonists & inhibitors; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology; D017154:Stromal Cells; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
D000970:Antineoplastic Agents; D012739:Gonadal Steroid Hormones; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein; D051523:Fibroblast Growth Factor 7; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3