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mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis.
- Source :
-
Scientific Reports . 9/28/2018, Vol. 8 Issue 1, p1-1. 1p. - Publication Year :
- 2018
-
Abstract
- Skeletal osteoblasts are important regulators of B-lymphopoiesis, serving as a rich source of factors such as CXCL12 and IL-7 which are crucial for B-cell development. Recent studies from our laboratory and others have shown that deletion of Rptor, a unique component of the mTORC1 nutrient-sensing complex, early in the osteoblast lineage development results in defective bone development in mice. In this study, we now demonstrate that mTORC1 signalling in pre-osteoblasts is required for normal B-lymphocyte development in mice. Targeted deletion of Rptor in osterix-expressing pre-osteoblasts (Rptorob−/−) leads to a significant reduction in the number of B-cells in the bone marrow, peripheral blood and spleen at 4 and 12 weeks of age. Rptorob−/− mice also exhibit a significant reduction in pre-B and immature B-cells in the BM, indicative of a block in B-cell development from the pro-B to pre-B cell stage. Circulating levels of IL-7 and CXCL12 are also significantly reduced in Rptorob−/− mice. Importantly, whilst Rptor-deficient osteoblasts are unable to support HSC differentiation to B-cells in co-culture, this can be rescued by the addition of exogenous IL-7 and CXCL12. Collectively, these findings demonstrate that mTORC1 plays an important role in extrinsic osteoblastic regulation of B-cell development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Scientific Reports
- Publication Type :
- Academic Journal
- Accession number :
- 132044461
- Full Text :
- https://doi.org/10.1038/s41598-018-32858-5