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- 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.
- Authors
Nianlan Yang; Baban, Babak; Isales, Carlos M.; Xing-Ming Shi
- Abstract
Bone marrow is a reservoir for regulatory T (Treg) cells, but how Treg 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 Treg 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 Treg cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and Treg 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.
- Subjects
BONE marrow; MESENCHYMAL stem cells; T cells; GLUCOCORTICOIDS; LEUCINE zippers
- Publication
FASEB Journal, 2015, Vol 29, Issue 9, p3954
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.15-273664