Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus. Issue 10 (5th September 2014)

• Record Type: Journal Article
• Authors: Ribeiro, Ana R.; Meireles, Catarina; Rodrigues, Pedro M.; Alves, Nuno L.
• Is Part Of: European journal of immunology. Volume 44:Issue 10(2014:Oct.)
• Page Start: 2918
• Page End: 2924
• Publication Date: 2014-09-05
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201444585
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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<sup>hi</sup>) develop normally in immunocompetent and <italic>Rag2</italic><sup>−/−</sup>thymi, their differentiation is partially blocked in <italic>Rag2</italic><sup>−/−</sup><italic>Il2rg</italic><sup>−/−</sup> 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 <italic>Ulex europaeus</italic> agglutinin 1 (UEA)<sup>+</sup> mTEC subtypes expressing intermediate CCRL1 levels (CCRL1<sup>int</sup>) that conspicuously emerge in the postnatal thymus and differentially express <italic>Tnfrsf11a</italic>, <italic>Ccl21</italic>, and <italic>Aire</italic>. While rare in fetal and in <italic>Rag2</italic><sup>−/−</sup> thymi, CCRL1<sup>int</sup> mTECs are restored in <italic>Rag2</italic><sup>−/−</sup>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.</p> </abstract>