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2016 ; 46
(4
): 857-62
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Relb acts downstream of medullary thymic epithelial stem cells and is essential
for the emergence of RANK(+) medullary epithelial progenitors
#MMPMID26806881
Baik S
; Sekai M
; Hamazaki Y
; Jenkinson WE
; Anderson G
Eur J Immunol
2016[Apr]; 46
(4
): 857-62
PMID26806881
show ga
Thymic epithelial cells (TECs) provide essential signals for ??T-cell
development, and medullary TECs (mTECs) control T-cell tolerance through both
negative selection and Foxp3(+) regulatory T (Treg) cell development. Although
heterogeneity within the mTEC compartment is well studied, the molecular
regulators of specific stages of mTEC development are still poorly understood.
Given the importance of the RANK-RANKL axis in thymus medulla formation, we have
used RANK Venus reporter mice to analyze the ontogeny of RANK(+) TECs during
development and correlated RANK expression with mTEC stem cells defined by
SSEA-1. In addition, we have investigated how requirements for the key regulators
Foxn1 and Relb map to specific stages of mTEC development. Here, we show
SSEA-1(+) mTEC stem cells emerge prior to RANK expression and are present in both
nude and Relb(-/-) mice, providing direct evidence that mTEC lineage
specification occurs independently of Foxn1 and Relb. In contrast, we show that
Relb is necessary for the effective production of downstream RANK(+) mTEC
progenitors. Collectively, our work defines stage-specific requirements for
critical TEC regulators during medulla development, including the timing of Relb
dependency, and provides new information on mechanisms controlling mTEC
specification.
|Animals
[MESH]
|Cell Differentiation
[MESH]
|Cell Lineage/immunology
[MESH]
|Epithelial Cells/cytology
[MESH]
|Forkhead Transcription Factors/metabolism
[MESH]
|Lewis X Antigen/metabolism
[MESH]
|Mice
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Knockout
[MESH]
|Mice, Nude
[MESH]
|Receptor Activator of Nuclear Factor-kappa B/*metabolism
[MESH]