Donor-specific (DST) or nonspecific blood transfusions administered before transplantation can enhance survival of vascularized allografts both in humans and animals but the immunological mechanisms of this effect remain unclear. We have analyzed the expression and the role of endogenous TGFb 1 in a model of heart allograft tolerance, induced by pregraft DST in adult rats. We reported previousl...

The goal of the present study was to determine the molecular mechanism whereby transforming growth factor b (TGFb) increases smooth muscle (SM) a-actin expression. Confluent, growth-arrested rat aortic smooth muscle cells (SMC) were transiently transfected with various SM a-actin promoter/chloramphenicol acetyltransferase deletion mutants and stimulated with TGFb (2.5 ng/ml). Results demonstrat...

Transforming Growth Factor-beta (TGFb) and activin A (actA) are members of the TGFb superfamily and display overlapping biological activities, including the ability to promote the conversion of conventional CD4 T cells to regulatory T cells (Tregs). We have recently shown that in situ vaccination by local tumor irradiation is hindered by activation of latent TGFb (Vanpouille-Box et al., Cancer ...

A TGFb-like signal is required for spicule development in Caenorhabditis elegans males. This signal appears to originate in the male-specific musculature and is required for the migrations of cells within the proctodeum. The migrations of these cells form cellular molds, the spicule traces, in which the cuticle of the spicules is secreted. Mutations in daf-4, sma-2, sma-3, and sma-4, which disr...

Factors influencing the development of CD41CD251 T-cells in vivo are poorly understood. In order to investigate the contribution of TGFb1 to the development and function of CD41CD251 T-cells, we generated a gain of function mutation resulting in the overexpression of an active form of TGFb1 in T-cells under control of the human CD2 promoter. In peripheral lymphoid organs and in the thymus, the ...

Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor B (TGFB)-1, which is activated by radiation, is a potent and pleiotropic mediator of physiologic and pathologic processes. Here we show that TGFB inhibition impedes the canonical cellular DNA damage s...

Background Transforming Growth Factor beta (TGFb) is a highly pleiotropic cytokine that is involved in numerous signalling pathways, including immune homeostasis. It is secreted by all immune cell lineages and is classically viewed as an anti-inflammatory cytokine. TGFb is associated with regulatory T cell (Treg) induction, and Tregfunction. However, in combination with pro-inflammatory cytokin...

Acquired resistance to TGFb is a key step in the early stages of tumorigenesis. Mutations in TGFb signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of crosstalk between these two pathways throug...

During the course of breast cancer progression, normally dormant tumour-promoting effects of transforming growth factor b (TGFb), including migration, invasion, and metastasis are unmasked. In an effort to identify mechanisms that regulate the pro-migratory TGFb ‘switch’ in mammary epithelial cells in vitro, we found that TGFb stimulates the phosphorylation of Smad1 and Smad5, which are typical...

Tissue homeostasis in mammals relies on powerful cytostatic and differentiation signals delivered by the cytokine TGFb and relayed within the cell via the activation of Smad transcription factors. Formation of transcription regulatory complexes by the association of Smad4 with receptor-phosphorylated Smads 2 and 3 is a central event in the canonical TGFb pathway. Here we provide evidence for a ...