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Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus.
- Source :
- European Journal of Immunology; Oct2014, Vol. 44 Issue 10, p2918-2924, 7p
- Publication Year :
- 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<superscript>hi</superscript>) develop normally in immunocompetent and Rag2<superscript>−/−</superscript>thymi, their differentiation is partially blocked in Rag2<superscript>−/−</superscript> Il2rg<superscript>−/−</superscript> 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)<superscript>+</superscript> mTEC subtypes expressing intermediate CCRL1 levels (CCRL1<superscript>int</superscript>) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2<superscript>−/−</superscript> thymi, CCRL1<superscript>int</superscript> mTECs are restored in Rag2<superscript>−/−</superscript>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 44
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 98836704
- Full Text :
- https://doi.org/10.1002/eji.201444585