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 (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.—Yang, N., Baban, B., Isales, C. M., Shi, X.‐M. Crosstalk between bone marrow‐derived mesenchymal stem cells and regulatory T cells through a glucocorticoid‐induced leucine zipper/developmental endothelial locus‐1‐dependent mechanism. FASEB J. 29, 3954‐3963 (2015). www.fasebj.org