Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren’s syndrome
Open Access
- 5 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (3), 1-14
- https://doi.org/10.1038/s41419-020-2359-6
Abstract
Mesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren’s syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice. Mechanistically, we show that ID3 negatively regulated BMP4 expression by preventing binding of basic helix–loop–helix protein E2A to the promoter of the Bmp4 gene. BMP4 in turn promoted PGE2 production in MSCs, and exhibited enhanced suppressive activities of T-cell proliferation and Th1 differentiation. Importantly, BMMSCs from SS patients showed significantly lower BMP4 and PGE2 expression than those from healthy individuals. Taken together, our findings revealed the targeting Id3 may be therapeutically useful for improving MSC immunoregulation and effectiveness of MSCs therapy for SS.Keywords
This publication has 45 references indexed in Scilit:
- Id proteins synchronize stemness and anchorage to the niche of neural stem cellsNature, 2012
- Prostaglandin E2 and T cells: friends or foes?Immunology & Cell Biology, 2011
- Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosisNature, 2011
- Modeling Sjögren's syndrome with Id3 conditional knockout miceImmunology Letters, 2011
- Control of the differentiation of regulatory T cells and TH17 cells by the DNA-binding inhibitor Id3Nature Immunology, 2010
- Allogeneic Periodontal Ligament Stem Cell Therapy for Periodontitis in SwineThe International Journal of Cell Cloning, 2010
- Genome-wide association identifies multiple ulcerative colitis susceptibility lociNature Genetics, 2010
- Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility lociNature Genetics, 2009
- Autoregulation of Th1-mediated inflammation by twist1 The Journal of Experimental Medicine, 2008
- Twist mediates suppression of inflammation by type I IFNs and AxlThe Journal of Experimental Medicine, 2006