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 struc...

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Bibliographic Details
Published in:Current opinion in pharmacology 2010-08, Vol.10 (4), p.425-433
Main Authors: Heng, Tracy SP, Chidgey, Ann P, Boyd, Richard L
Format: Article
Language:English
Subjects:
Aging - immunology
Aging - physiology
Animals
Antineoplastic Agents - toxicity
Atrophy - chemically induced
Epithelial Cells
Fibroblast Growth Factor 7 - pharmacology
fms-Like Tyrosine Kinase 3 - metabolism
Gonadal Steroid Hormones - antagonists & inhibitors
Growth Hormone - pharmacology
Humans
Insulin-Like Growth Factor I - pharmacology
Interleukin-7 - pharmacology
Internal Medicine
Medical Education
Membrane Proteins - pharmacology
Stem Cells - physiology
Stromal Cells
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - physiology
Thymus Gland - drug effects
Thymus Gland - immunology
Thymus Gland - physiology
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Summary: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.
ISSN:1471-4892
1471-4973
DOI:10.1016/j.coph.2010.04.006