TGF-beta type III receptor (T beta RIII) is a co-receptor for TGF beta family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-beta s, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that T beta RIII modulates T cell development by protecting developing thymocytes from apoptosis, however the role of this co-receptor in peripheral lymphocytes still remains elusive. Here we describe a detailed characterization of T beta RIII expression in murine and human lymphocyte subpopulations demonstrating that this co-receptor is significantly expressed in T but not B lymphocytes and among them, preferentially expressed on nave and central memory T cells. T beta RIII was upregulated after TCR stimulation, in parallel to other early activation markers. In contrast, natural and induced Tregs downregulated T beta RIII in association with FoxP3 upregulation. Finally, anti-T beta RIII blocking experiments demonstrated that T beta RIII promotes TGF beta-dependent iTreg conversion in vitro, and suggest that this co-receptor may be involved in modulating peripheral T cell tolerance and could be considered as a potential target to boost T cell immune responses. (C) 2017 Published by Elsevier Inc.