title: The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis.
abstract: 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.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Martínez
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sacedón
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Hidalgo
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Jaris
authors.initials: J
authors.lastname: Valencia
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Fernández-Sevilla
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Hernández-López
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Vicente
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Varas
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*
chemical_list: D019485:Bone Morphogenetic Proteins; C508594:IL2 protein, human; C508605:IL7 protein, human; D007376:Interleukin-2; D015851:Interleukin-7; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D052005:Bone Morphogenetic Protein Receptors, Type I