The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis

Bone Morphogenetic Proteins (BMPs) form a group of secreted factors that belongs to the TGF-β superfamily. Among different roles in a number of immune cell types, BMPs are known to regulate T cell development within the thymus, although the role of BMP signaling in human mature T cells remains elusive. In this study, we demonstrate that canonical BMP signaling is necessary during two critical events that regulate the size and function of human naive CD4⁺ T cell population: activation and homeostasis. Upon stimulation via TCR, naive CD4⁺ T cells upregulate the expression of BMP ligands triggering canonical BMP signaling in CD25⁺ cells. Blockade of BMP signaling severely impairs CD4⁺ T cell proliferation after activation mainly through regulation of IL-2, since the addition of this cytokine recuperates normal T cell expansion after inhibition of BMP signaling. Similarly, activation of canonical BMP pathway is required for both the maintenance of cell survival and the homeostatic proliferation induced by IL-7, a key factor for T cell homeostasis. Moreover, upregulation of two critical receptors for T cell homeostasis, CXCR4 and CCR9, triggered by IL-7 is also abrogated in the absence of BMP signaling. Collectively, we describe important roles of the canonical BMP signaling in human naive CD4⁺ T cell activation and homeostasis that could be valuable for clinical application.