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2016 ; 5
(11
): 1496-1505
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Autophagy Improves the Immunosuppression of CD4+ T Cells by Mesenchymal Stem
Cells Through Transforming Growth Factor-?1
#MMPMID27400793
Gao L
; Cen S
; Wang P
; Xie Z
; Liu Z
; Deng W
; Su H
; Wu X
; Wang S
; Li J
; Ouyang Y
; Wu Y
; Shen H
Stem Cells Transl Med
2016[Nov]; 5
(11
): 1496-1505
PMID27400793
show ga
: Mesenchymal stem cells (MSCs) have been extensively investigated as a promising
approach to treat many autoimmune and inflammatory diseases. The stress condition
would affect the therapeutic efficacy and induce autophagy of MSCs. However,
whether autophagy would affect the immunosuppressive capacity of MSCs is largely
unknown. The present study aimed to assess whether autophagy plays an important
role in regulating the immunomodulation of MSCs and the undermechanisms. We
successfully inhibited and induced autophagy of MSCs using 3-methyladenine (3-MA)
and rapamycin, respectively. Our results demonstrated that rapamycin strengthened
the capacity of MSCs to inhibit CD4(+) T-cell proliferation, whereas 3-MA
weakened the inhibitory ability of MSCs. Mechanistically, 3-MA-pretreated MSCs
secreted less, whereas rapamycin-pretreated MSCs secreted more transforming
growth factor-?1 (TGF-?1) compared with the control cells. Furthermore, exogenous
TGF-?1 addition recovered the immunosuppressive capacity of 3-MA-pretreated MSCs,
whereas exogenous anti-TGF-?1 antibody addition reduced the immunosuppressive
capacity of rapamycin-pretreated MSCs. These results indicated that the autophagy
level regulates the immunosuppression of CD4(+) T cells by MSCs through affecting
TGF-?1 secretion and provides a novel method for improving the therapeutic
efficacy of MSCs by activating autophagy. SIGNIFICANCE: Mesenchymal stem cell
(MSC)-based therapy is a promising tool to treat many diseases. Autophagy
occurred in MSCs during their application, especially in those exposed to stress
conditions. However, whether autophagy will affect the therapeutic efficacy of
MSCs is largely unknown. This study makes a significant contribution to
demonstrate that autophagy could improve the immunosuppression of CD4(+) T cells
by mesenchymal stem cells through transforming growth factor-?1. Therefore,
regulation of autophagy in MSCs would provide a promising strategy to improve the
therapeutic efficacy of these cells.