Brain derived neurotrophic factor enhances the role of mesenchymal stem cells in inhibiting follicular helper T cells / 中华血液学杂志

ABSTRACT

Objective@#To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells).@*Methods@#The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4+CXCR5+ Tfh cells and their subtypes were detected by flow cytometry.@*Results@#①The concentrations of IL-10, TGF-β, and IDO in the supernatant of BDNF group (BDNF-stimulated MSC) were higher than those of the control ones (adding PBS with the same volume) [IL-10 (42.1±4.4) ng/ml vs (19.3±2.1) ng/ml, t=4.761, P=0.009; TGF-β (13.9±1.7) ng/ml vs (5.3±0.6) ng/ml, t=5.129, P=0.008; IDO (441.3±56.9) ng/ml vs (226.7±37.6) ng/ml, t=3.130, P=0.035]; ②The comparisons between BDNF (co-culture of lymphocyte and BDNF-stimulated MSC) and MSC groups (co-culture of lymphocyte and MSC) were detailed as of follows the proportion of CD4+ CXCR5+Tfh cells were lower [(3.37±0.21)% vs (6.51±0.27)%, t=9.353, P<0.001], the proportion of CD4+ CXCR5+CXCR3+ CCR6- Tfh cells were higher [(41.14±2.04)% vs (26.72±2.57)%, t=4.383, P=0.012], CD4+CXCR5+CXCR3-CCR6- Tfh2 cells and CD4+CXCR5+CXCR3-CCR6+ Tfh17 cells were lower [Tfh2 (30.16±5.38)% vs (43.26±4.11)%, t=4.426, P=0.012; Tfh17 (15.61±1.52)% vs (22.32±0.72)%, t=4.202, P=0.014], the proportion of CD4+CXCR5+Foxp3+ Tfr cells were higher [(4.95±0.22)% vs (2.32±0.16)%, t=10.241, P<0.001], the concentration of IL-21 in the lymphocyte supernatant was lower [(0.28±0.03) ng/ml vs (0.85±0.08) ng/ml, t=6.675, P=0.003].@*Conclusion@#BDNF could enhance the inhibitory effect of MSC on Tfh cells through inhibiting the increasing of Tfh cells and the differentiations of Tfh2 and Tfh17 cells.