Abstract
Thymocyte development is a non-cell-autonomous process that requires signals provided by the thymic stroma. Bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) derived from thymic stroma have been implicated as possible regulators of T-cell development. Using thymic organ culture, this study demonstrates that both BMP4 and FGF7/FGF10 arrest early T-cell development at the CD4-CD8-CD44 +CD25- (double-negative 1 [DN1]) population and at the CD4-CD8- double-negative (DN) to CD4+CD8 + double-positive (DP) transition in a stromal compartment-dependent manner. Furthermore, BMP4 functions upstream of FGF7/FGF10, as the effects of BMP can be suppressed by cotreatment with an FGF receptor antagonist. BMP4 also acts directly on the thymic stroma to up-regulate the stroma-specific transcription factor Foxn1 and stroma-expressed chemokines. Taken together, the data in this report demonstrate that BMP acts upstream of FGF in the regulation of early T-cell development and that BMP4 acts primarily through the thymic stroma, thereby altering the thymic microenvironment and affecting thymopoiesis.
Original language | English (US) |
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Pages (from-to) | 3947-3953 |
Number of pages | 7 |
Journal | Blood |
Volume | 102 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2003 |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology