Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/114506
Author(s): Ribeiro, AR
Meireles, C
Rodrigues, PM
Alves, NL
Title: Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus.
Publisher: Wiley-VCH Verlag
Issue Date: 2014
Abstract: Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T-cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL-7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C-C motif) receptor-like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1(hi) ) develop normally in immunocompetent and Rag2(-/-) thymi, their differentiation is partially blocked in Rag2(-/-) Il2rg(-/-) counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross-talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)(+) mTEC subtypes expressing intermediate CCRL1 levels (CCRL1(int) ) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2(-/-) thymi, CCRL1(int) mTECs are restored in Rag2(-/-) Marilyn TCR-Tg mice, indicating that the appearance of postnatal-restricted mTECs is closely linked with T-cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.
Subject: Animals
Biomarkers/analysis
Cell Differentiation/immunology
Epithelial Cells/cytology
Flow Cytometry
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Receptors, CCR/biosynthesis
Receptors, CCR/immunology
T-Lymphocytes/cytology
T-Lymphocytes/immunology
Thymus Gland/cytology
Thymus Gland/growth & development
Thymus Gland/immunology
Transcriptome
URI: http://hdl.handle.net/10216/114506
Source: European journal of immunology, vol. 44(10), p. 2918-2924
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/117057/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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