RT Journal Article
SR Electronic
T1 Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 5496
OP 5504
DO 10.4049/jimmunol.169.10.5496
VO 169
IS 10
A1 Hager-Theodorides, Ariadne L.
A1 Outram, Susan V.
A1 Shah, Divya K.
A1 Sacedon, Rosa
A1 Shrimpton, Rachel E.
A1 Vicente, Angeles
A1 Varas, Alberto
A1 Crompton, Tessa
YR 2002
UL http://www.jimmunol.org/content/169/10/5496.abstract
AB Bone morphogenetic protein (BMP)2 and BMP4 are involved in the development of many tissues. In this study, we show that BMP2/4 signaling is involved in thymocyte development. Our data suggest that termination of BMP2/4 signaling is necessary for differentiation of CD44+CD25−CD4−CD8− double negative (DN) cells along the T cell lineage. BMP2 and BMP4 are produced by the thymic stroma and the requisite BMP receptor molecules (BMPR-1A, BMPR-1B, BMPR-II), and signal transduction molecules (Smad-1, -5, -8, and -4) are expressed by DN thymocytes. BMP4 inhibits thymocyte proliferation, enhances thymocyte survival, and arrests thymocyte differentiation at the CD44+CD25− DN stage, before T cell lineage commitment. Neutralization of endogenous BMP2 and BMP4 by treatment with the antagonist Noggin promotes and accelerates thymocyte differentiation, increasing the expression of CD2 and the proportion of CD44−CD25− DN cells and CD4+CD8+ double-positive cells. Our study suggests that the BMP2/4 pathway may function in thymic homeostasis by regulating T cell lineage commitment and differentiation.