Document details
Intrathymic deletion of IL-7 reveals a contribution of the bone marrow to thymic rebound induced by androgen blockade(Article)(Open Access)
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- aInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal
- bThymus Development and Function Laboratory, Institute for Molecular and Cellular Biology, Porto, 4200-135, Portugal
- cDoctoral Program in Biomedical Sciences, Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, 4050-313, Portugal
- dInnate Immunity Unit, Pasteur Institute, Paris, 75724, France
- eINSERM U1223, Paris, 75015, France
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Abstract
Despite the well-documented effect of castration in thymic regeneration, the singular contribution of the bone marrow (BM) versus the thymus to this process remains unclear. The chief role of IL-7 in pre- and intrathymic stages of T lymphopoiesis led us to investigate the impact of disrupting this cytokine during thymic rebound induced by androgen blockade. We found that castration promoted thymopoiesis in young and aged wild-type mice. In contrast, only young germline IL-7–deficient (Il7 2 / 2 ) mice consistently augmented thymopoiesis after castration. The increase in T cell production was accompanied by the expansion of the sparse medullary thymic epithelial cell and the peripheral T cell compartment in young Il7 2 / 2 mice. In contrast to young Il7 2 / 2 and wild-type mice, the poor thymic response of aged Il7 2 / 2 mice after castration was associated with a defect in the expansion of BM hematopoietic progenitors. These findings suggest that BM-derived T cell precursors contribute to thymic rebound driven by androgen blockade. To assess the role of IL-7 within the thymus, we generated mice with conditional deletion of IL-7 (Il7 conditional knockout [cKO]) in thymic epithelial cells. As expected, Il7cKO mice presented a profound defect in T cell development while maintaining an intact BM hematopoietic compartment across life. Unlike Il7 2 / 2 mice, castration promoted the expansion of BM precursors and enhanced thymic activity in Il7cKO mice independently of age. Our findings suggest that the mobilization of BM precursors acts as a prime catalyst of castration-driven thymopoiesis. The Journal of Immunology, 2018, 200: 1389–1398. Copyright © 2018 by The American Association of Immunologists, Inc.
Indexed keywords
| EMTREE drug terms: | androgeninterleukin 7interleukin 7interleukin-7, mouse |
|---|---|
| EMTREE medical terms: | ageanimal cellanimal experimentanimal modelanimal tissueArticlebone marrowcastrationcontrolled studyepithelium cellgene deletiongerm linehematopoietic stem cellknockout mouselymphopoiesismalemousenonhumanpriority journalprotein functionT lymphocytethymic medullathymopoiesisthymusanimalbone marrow cellC57BL mousecell differentiationcytologydeficiencyimmunologymetabolismphysiologythymus |
| MeSH: | AndrogensAnimalsBone Marrow CellsCastrationCell DifferentiationHematopoietic Stem CellsInterleukin-7LymphopoiesisMaleMiceMice, Inbred C57BLMice, KnockoutThymus Gland |
Chemicals and CAS Registry Numbers:
Androgens; Interleukin-7; interleukin-7, mouse
Funding details
| Funding sponsor | Funding number | Acronym |
|---|---|---|
| Programa Operacional Temático Factores de Competitividade | ||
| POCI-01-0145-FEDER-007274 | ||
| Fundação para a Ciência e a Tecnologia See opportunities | PTDC/SAU-IMU/117057/2010,NORTE-01-0145-FEDER-000012,FCOMP-01-0124-FEDER-021075 | |
| NORTE 2020 | ||
| European Regional Development Fund | ||
| European Research Council | ||
| Ministério da Ciência, Tecnologia e Ensino Superior | ||
| Fundação para a Ciência e a Tecnologia See opportunities | ||
| Horizon 2020 | 2020,637843-TEC_Pro | |
| European Regional Development Fund | ||
| European Research Council | ||
| Horizon 2020 | 695467-ILC_REACTIVITY | |
| Institut Pasteur | ||
| Fundação para a Ciência e a Tecnologia See opportunities | ||
| Institut National de la Santé et de la Recherche Médicale |
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1
This work was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (Grant 637843-TEC_Pro) (to N.L.A.); Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the Operational Competitiveness Program–COMPETE; National Funds through the Fundac¸ão para a Ciência e a Tecnologia (FCT) under Project FCOMP-01-0124-FEDER-021075 (Grant PTDC/SAU-IMU/117057/2010); NORTE-01-0145-FEDER-000012–Structured Program on Bioengineered Therapies for Infectious Diseases and Tissue Regeneration, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER); FEDER funds through the COMPETE 2020–Operational Program for Competitiveness and Internationalization, Portugal 2020; and Portuguese funds through the FCT/Ministério da Ciência, Tecnologia e Inovac¸ão in the framework of the project Institute for Research and Innovation in Health Sciences (Grant POCI-01-0145-FEDER-007274).
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2
This study was also supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (Grant 695467-ILC_REACTIVITY) (to J.P.D.S.). N.L.A., P.M.R., A.R.R., and C.M. received funding from the Investigator Program and doctoral fellowships from the FCT. J.P.D.S. and N.S. received funding from the Institut Pasteur and INSERM.
- ISSN: 00221767
- CODEN: JOIMA
- Source Type: Journal
- Original language: English
- DOI: 10.4049/jimmunol.1701112
- PubMed ID: 29321277
- Document Type: Article
- Publisher: American Association of Immunologists
Alves, N.L.; Instituto de Investigação e Inovação em Saúde (I3S), Instituto de Biologia Molecular e Celular (IBMC), Rua Alfredo Allen, 208, Porto, Portugal;
© Copyright 2019 Elsevier B.V., All rights reserved.
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