PT  - JOURNAL ARTICLE
AU  - Hager-Theodorides, Ariadne L.
AU  - Outram, Susan V.
AU  - Shah, Divya K.
AU  - Sacedon, Rosa
AU  - Shrimpton, Rachel E.
AU  - Vicente, Angeles
AU  - Varas, Alberto
AU  - Crompton, Tessa
TI  - Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation
AID  - 10.4049/jimmunol.169.10.5496
DP  - 2002 Nov 15
TA  - The Journal of Immunology
PG  - 5496--5504
VI  - 169
IP  - 10
4099  - http://www.jimmunol.org/content/169/10/5496.short
4100  - http://www.jimmunol.org/content/169/10/5496.full
SO  - J. Immunol.2002 Nov 15; 169
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.