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LncRNA H19 induces immune dysregulation of BMMSCs, at least partly, by inhibiting IL-2 production
- Source :
- Molecular Medicine, Molecular Medicine, Vol 27, Iss 1, Pp 1-11 (2021)
- Publication Year :
- 2021
- Publisher :
- BioMed Central, 2021.
-
Abstract
- Background Systemic lupus erythematosus (SLE) is a representative systemic autoimmune disease. LncRNA H19 has been identified to participate in various biological processes in human diseases. However, the role of H19 in SLE remains unclear. Methods In this study, we first examined H19 expression in SLE patients by RT-qPCR and found that H19 expression was significantly upregulated in the serum and bone marrow-derived mesenchymal stem cells (BMMSCs) of SLE patients and positively associated with SLE disease activity index. We then performed gain-of-function and loss-of-function using mimic-H19 (H19-OE) and inhibitor-H19 (H19-KD) to examine the effects of H19 on BMMSC differentiation, proliferation, migration, and apoptosis using flow cytometry, DAPI staining, and migration and apoptosis assays. Results The results showed that H19 inhibited proliferation and migration but promoted apoptosis of BMMSCs, interfered with BMMSCs-mediated Treg cell proliferation and differentiation, and regulated BMMSCs-mediated Tfh/Treg cell balance. Dual-luciferase reporter assay confirmed the in silico prediction of interaction between H19 and IL-2. Furthermore, RT-qPCR showed that H19 directly inhibited IL-2 transcription in BMMSCs. ELISA showed that both active and total IL-2 protein levels were significantly lower in SLE BMMSCs. More importantly, we found that IL-2 significantly enhanced H19-OE-induced Treg cell differentiation and migration of BMMSCs, and these effects were reversed by anti-IL-2 antibody. Conclusion Overall, our study indicates that LncRNA H19 induces immune dysregulation of BMMSCs, at least partly, by inhibiting IL-2 production and might be a novel therapeutic target for SLE.
- Subjects :
- 0301 basic medicine
Apoptosis
medicine.disease_cause
T-Lymphocytes, Regulatory
Biochemistry
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Lupus Erythematosus, Systemic
Genetics (clinical)
Cells, Cultured
biology
medicine.diagnostic_test
Cell Differentiation
female genital diseases and pregnancy complications
lncRNA H19
030220 oncology & carcinogenesis
embryonic structures
Molecular Medicine
RNA, Long Noncoding
Disease Susceptibility
Antibody
Research Article
Immune regulation
RM1-950
QD415-436
Flow cytometry
Immunomodulation
03 medical and health sciences
Systemic lupus erythematosus
Downregulation and upregulation
Genetics
medicine
Humans
DAPI
Molecular Biology
IL-2
Mesenchymal stem cell
Mesenchymal Stem Cells
Immune dysregulation
Molecular medicine
Coculture Techniques
030104 developmental biology
chemistry
Gene Expression Regulation
Case-Control Studies
biology.protein
Cancer research
Leukocytes, Mononuclear
Interleukin-2
Therapeutics. Pharmacology
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 15283658 and 10761551
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine
- Accession number :
- edsair.doi.dedup.....795cc882a1882be129d972de25ada32e