Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade.

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 ^-/- ) 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 ^-/- mice. In contrast to young Il7 ^-/- and wild-type mice, the poor thymic response of aged Il7 ^-/- 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 ^-/- 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.
(Copyright © 2018 by The American Association of Immunologists, Inc.)