The CD200/CD200R mechanism in mesenchymal stem cells' regulation of dendritic cells

Yulei Zhao; Guohong Su; Qing Wang; Ruihuan Wang; Minjuan Zhang

The CD200/CD200R mechanism in mesenchymal stem cells' regulation of dendritic cells

Am J Transl Res. 2021 Aug 15;13(8):9607-9613. eCollection 2021.

Authors

Yulei Zhao¹, Guohong Su¹, Qing Wang¹, Ruihuan Wang¹, Minjuan Zhang¹

Affiliation

¹ The Second Department of Hematology, Cangzhou Central Hospital 16 West Xinhua Road, Yunhe, Cangzhou, China.

PMID: 34540085
PMCID: PMC8430165

Abstract

Objective: To investigate the CD200/CD200R pathway mechanism in mesenchymal stem cells' (MSC) regulation of dendritic cells (DC) (MSc).

Methods: We collected marrow samples from 40 patients admitted to our hospital from January 2018 to December 2019. The bone marrow MSCs were cultivated, and the peripheral blood mononuclear cells (PBMC) and peripheral blood DC were isolated to establish an in vitro immune response model. The expressions of the CD200 molecule on the surface of MSC were measured. Anti-CD200 blocking antibodies were added to the culture system to observe the effect of the PBMC differentiation and the immature DC (imDC) to mature DC (mDC). Then the impact of the different positive rates of CD200 in the same MSC on imDC maturity was measured.

Results: After adding mitogen pHA, the IL-4, IL-10, and TNF-α secretions were increased (all P<0.05), and the OD value of the PBMC+pHA group was higher than it was in the PBMC group. After stimulated by pHA, the CD200 of the MSC group was higher than it was in the MSC+PBMC group (P<0.05). The MSC+PBMC group co-culture inhibited the development of imDC to mDC. Adding anti-CD200 antibodies to the MSC+PBMC co-culture system, MSC could still inhibit the differentiation of PBMC to imDC, and MSC had a significant inhibition effect on imDC to mDC maturation (P=0.006). The addition of MSC reduces the maturation markers on the surface of mDC (P<0.05). The addition of MSC inhibited the ability of mDC to stimulate PBMC (P_OD<0.05) and decreased the IL-12 (P_IL-12<0.05) levels. The addition of the anti-CD200 antibody increased the proliferation ability of mDC to stimulate PBMC (P_OD<0.05), and it also increased the IL-12 levels in mDC (P_IL-12<0.05). The expression of the DC mature immune phenotype in the CD200 high expression group was weak (P_{CD83, CD86}<0.05).

Conclusion: The mechanism by which MSC inhibits DC may be achieved through the CD200/CD200R pathway, and the CD200/CD200R pathway mainly acts on the process from imDC to mDC.

Keywords: CD200/CD200R; Mesenchymal stem cells; dendritic cells.