Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors

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@article{d3f439db81654ed8a116631f237b1a20,
title = "Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors",
abstract = "In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of first cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κB (RANK). In vivo analysis reveals the capacity of CD205 TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts.",
keywords = "Cellular immunology, Developmental immunology, Thymic epithelial cells",
author = "Song Baik and Jenkinson, {Eric J} and Lane, {Peter J L} and Graham Anderson and William Jenkinson",
note = "{\textcopyright} 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2013",
month = mar,
doi = "10.1002/eji.201243209",
language = "English",
volume = "43",
pages = "589--94",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "3",

}

RIS

TY - JOUR

T1 - Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors

AU - Baik, Song

AU - Jenkinson, Eric J

AU - Lane, Peter J L

AU - Anderson, Graham

AU - Jenkinson, William

N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2013/3

Y1 - 2013/3

N2 - In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of first cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κB (RANK). In vivo analysis reveals the capacity of CD205 TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts.

AB - In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of first cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κB (RANK). In vivo analysis reveals the capacity of CD205 TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts.

KW - Cellular immunology

KW - Developmental immunology

KW - Thymic epithelial cells

U2 - 10.1002/eji.201243209

DO - 10.1002/eji.201243209

M3 - Article

C2 - 23299414

VL - 43

SP - 589

EP - 594

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 3

ER -