Thymic crosstalk restrains the pool of cortical thymic epithelial cells with progenitor properties

Autor: Catarina Meireles, Nuno L. Alves, Rute D. Pinto, Pedro M. Rodrigues, Catarina Leitão, Ana R. Ribeiro
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Immunology
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 0014-2980
DOI: 10.1002/eji.201746922
Popis: Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs). These ClonoTECs are EpCAM+MHCII-Foxn1lo cells that lack traits of mature cTECs or mTECs but co-express stem-cell markers, including CD24 and Sca-1. Supportive of their progenitor identity, ClonoTECs reintegrate within native thymic microenvironments and generate cTECs or mTECs in vivo. Strikingly, the frequency of cTECs with the potential to generate ClonoTECs wanes between the postnatal and young adult immunocompetent thymus, but it is sustained in alymphoid Rag2-/-Il2rg-/- counterparts. Conversely, transplantation of wild-type bone marrow hematopoietic progenitors into Rag2-/-Il2rg-/- mice and consequent restoration of thymocyte-mediated TEC differentiation diminishes the frequency of colony-forming units within cTECs. Our findings provide evidence that the cortical epithelium contains a reservoir of epithelial progenitors whose abundance is dynamically controlled by continual interactions with developing thymocytes across lifespan. This work has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 637843 - TEC_Pro), from FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274) and FEDER funds through the Operational Competitiveness Programme - COMPETE and by National Funds through FCT - Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-021075 (PTDC/SAU-IMU/117057/2010). N.L.A., P.M.R., A.R.R., C.M., and R.D.P. are supported by the Investigator program, Post-doctoral and PhD fellowships from FCT (Portugal).
Databáze: OpenAIRE
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