Checkpoints in the development of thymic cortical epithelial cells

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Checkpoints in the development of thymic cortical epithelial cells. / Shakib, S; Desanti, Guillaume; Jenkinson, William; Parnell, SM; Jenkinson, Eric; Anderson, Graham.

In: Journal of Immunology, Vol. 182, No. 1, 01.01.2009, p. 130-7.

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@article{dbf1ebf3473e46fd88dd68fd121aa21e,
title = "Checkpoints in the development of thymic cortical epithelial cells",
abstract = "In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.",
author = "S Shakib and Guillaume Desanti and William Jenkinson and SM Parnell and Eric Jenkinson and Graham Anderson",
year = "2009",
month = jan,
day = "1",
language = "English",
volume = "182",
pages = "130--7",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

RIS

TY - JOUR

T1 - Checkpoints in the development of thymic cortical epithelial cells

AU - Shakib, S

AU - Desanti, Guillaume

AU - Jenkinson, William

AU - Parnell, SM

AU - Jenkinson, Eric

AU - Anderson, Graham

PY - 2009/1/1

Y1 - 2009/1/1

N2 - In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.

AB - In the thymus, interactions between immature thymocytes and thymic epithelial cells (TECs) regulate the development and selection of self-tolerant MHC-restricted T cells. Despite the importance of cortical (cTEC) and medullary (mTEC) thymic epithelial cells in fostering T cell production, events in TEC development are still unclear. Although precursor-product relationships during mTEC development have been reported, and some genetic regulators of mTEC development have been identified, stages in cTEC development occurring downstream of recently identified bipotent cTEC/mTEC progenitors remain poorly defined. In this study, we combine analysis of differentiation, proliferation, and gene expression of TECs in the murine thymus, that has enabled us to identify cTEC progenitors, define multiple stages in cTEC development, and identify novel checkpoints in development of the cTEC lineage. We show an essential requirement for FoxN1 in the initial development of cTEC from bipotent progenitors, and demonstrate a stage-specific requirement for CD4(-)8(-) thymocytes in later stages of cTEC development. Collectively, our data establish a program of cTEC development that should provide insight into the formation and function of the thymic cortex for T cell development.

M3 - Article

C2 - 19109143

VL - 182

SP - 130

EP - 137

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -