title: Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism.
abstract: Bone marrow is a reservoir for regulatory T (T(reg)) cells, but how T(reg) cells are regulated in that environment remains poorly understood. We show that expression of glucocorticoid (GC)-induced leucine zipper (GILZ) in bone marrow mesenchymal lineage cells or bone marrow-derived mesenchymal stem cells (BMSCs) increases the production of T(reg) cells via a mechanism involving the up-regulation of developmental endothelial locus-1 (Del-1), an endogenous leukocyte-endothelial adhesion inhibitor. We found that the expression of Del-1 is increased ∼4-fold in the bone tissues of GILZ transgenic (Tg) mice, and this increase is coupled with a significant increase in the production of IL-10 (2.80 vs. 0.83) and decrease in the production of IL-6 (0.80 vs. 2.33) and IL-12 (0.25 vs. 1.67). We also show that GILZ-expressing BMSCs present antigen in a way that favors T(reg) cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and T(reg) in the bone marrow microenvironment. These data, together with our previous findings that overexpression of GILZ in BMSCs antagonizes TNF-α-elicited inflammatory responses, suggest that GILZ plays important roles in bone-immune cell communication and BMSC immune suppressive functions.
authors.affiliation: *Department of Neuroscience and Regenerative Medicine, Department of Oral Biology, and Department of Orthopaedic Surgery, Georgia Regents University, Augusta, Georgia, USA.
authors.forename: Nianlan
authors.initials: N
authors.lastname: Yang
authors.affiliation: *Department of Neuroscience and Regenerative Medicine, Department of Oral Biology, and Department of Orthopaedic Surgery, Georgia Regents University, Augusta, Georgia, USA xshi@gru.edu bbaban@gru.edu.
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.affiliation: *Department of Neuroscience and Regenerative Medicine, Department of Oral Biology, and Department of Orthopaedic Surgery, Georgia Regents University, Augusta, Georgia, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.affiliation: *Department of Neuroscience and Regenerative Medicine, Department of Oral Biology, and Department of Orthopaedic Surgery, Georgia Regents University, Augusta, Georgia, USA xshi@gru.edu bbaban@gru.edu.
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Shi
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C498608:Dsip1 protein, mouse; C491706:Edil3 protein, mouse; C556062:IL10 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: bone loss; bone marrow microenvironment; immune suppressive