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Thymic epithelial cell-derived signals control B progenitor formation and proliferation in the thymus by regulating Let-7 and Arid3a.
- Source :
- PLoS ONE, Vol 13, Iss 2, p e0193188 (2018)
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus and have been recently shown to impact T cell selection, however, the mechanisms controlling B cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice, down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week after birth caused a dramatic reduction of T progenitors and an increase of B cell progenitors. This time point is coincident with the switch from fetal to adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7 system. We hypothesize that the thymic environment might regulate this process to suppress fetal-type B cell development in the thymus. In this study we show that in the Foxn1lacZ thymus, although the down-regulation of Lin28 in thymocytes was normal, up-regulation of Let-7 was impaired. The failure to up-regulate Let-7 caused a transient increase of Arid3a in B precursors, which is known to promote fetal-type B cell fate. Over-expression of Lin28a in HSCs also reduced Let-7 and promoted Arid3a expression in BM and thymic B progenitors, increasing B cell production in the thymus. The level of Let-7 in thymic B progenitors was up regulated by in vitro co-culture with IL15, Vitamin-D3, and retinoic acid, thus down-regulating Arid3a to promote B cell differentiation. All of these signals were produced in thymic epithelial cells (TECs) related to Let-7 expression in thymic B progenitors, and down-regulated in Foxn1lacZ mutants. Our data show that signals provided by TEC control thymic B cell development by up-regulating Let-7, suppressing Arid3a expression in intrathymic progenitor B cells to limit their proliferation during the neonatal to adult transition.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2823c547020341d986ec3d2f9519aa47
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0193188