BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis

Peter T. Tsai, Robert A. Lee, Hong Wu

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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 languageEnglish (US)
Pages (from-to)3947-3953
Number of pages7
JournalBlood
Volume102
Issue number12
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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