Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor, a Transforming Growth Factor beta Rheostat That Controls Murine Treg Cell/Th17 Cell Differentiation and the Development of Autoimmune Arthritis by Reducing Interleukin-2 Signaling

摘要

Objective. Transforming growth factor beta (TGF beta) plays a prominent role in the establishment of immunologic tolerance, and mice lacking TGF beta 1 die of multiorgan inflammation early in life. TGF beta controls the differentiation of CD4+ lymphocytes into Treg cells or proinflammatory Th17 cells. Although this dual capacity is modulated by the presence of additional cytokines around the activated cells, TGF beta also dissociates Th17/Treg cell differentiation in a dose-dependent manner by mechanisms still unknown. The purpose of this study was to explore the contribution of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) to the modulation of TGF beta activity during the differentiation of CD4+ cells and in the control of immunologic tolerance in mice with collagen-induced arthritis (CIA).