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Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Feb 15; Vol. 200 (4), pp. 1389-1398. Date of Electronic Publication: 2018 Jan 10. - Publication Year :
- 2018
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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 <superscript>-/-</superscript> ) 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 <superscript>-/-</superscript> mice. In contrast to young Il7 <superscript>-/-</superscript> and wild-type mice, the poor thymic response of aged Il7 <superscript>-/-</superscript> 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, Il7 cKO mice presented a profound defect in T cell development while maintaining an intact BM hematopoietic compartment across life. Unlike Il7 <superscript>-/-</superscript> mice, castration promoted the expansion of BM precursors and enhanced thymic activity in Il7 cKO mice independently of age. Our findings suggest that the mobilization of BM precursors acts as a prime catalyst of castration-driven thymopoiesis.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Androgens metabolism
Animals
Bone Marrow Cells immunology
Castration
Cell Differentiation physiology
Interleukin-7 deficiency
Interleukin-7 immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Thymus Gland cytology
Hematopoietic Stem Cells immunology
Lymphopoiesis physiology
Thymus Gland immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 200
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 29321277
- Full Text :
- https://doi.org/10.4049/jimmunol.1701112