Role of bone marrow-derived mesenchymal stem cell defects in CD8+ CD28- suppressor T-lymphocyte induction in patients with immune thrombocytopenia and associated mechanisms.

Abstract:

:Many immune dysfunctions participate in immune thrombocytopenia (ITP) pathogenesis, including numeric and functional defects in suppressor T (Ts) cells and immune-regulation abnormalities in mesenchymal stem cells (MSCs). Recent studies showed that MSCs can promote Ts cell differentiation. Thus, we compared the Ts cell induction ability of bone marrow-derived MSCs (BM-MSCs) between patients with ITP and normal controls (NCs), and examined the mechanism of this difference. Co-culture of CD8+ T cells with BM-MSCs revealed that BM-MSCs elevated Ts cell percentage and function, but the efficiency was lower in patients with ITP than in NCs. Blockade experiments showed that blockade of interleukin 6 (IL-6) partially reversed Ts cell induction by BM-MSCs. Addition of exogenous IL-6 down-regulated Ts cell apoptosis. Moreover, BM-MSCs enhanced IL-10 secretion and inhibition ability of Ts cells. IL-6 secretion, regulatory abilities of IL-10 expression in Ts cells, and the enhanced efficiency of Ts cells inhibition function by BM-MSCs were all decreased in patients with ITP. All-trans retinoic acid preconditioning promoted BM-MSC induction of Ts cell percentages and umbilical cord-derived (UC) MSCs efficiently improved ITP Ts cell numbers and dysfunction. In conclusion, defects of BM-MSCs in Ts cell induction are involved in ITP pathogenesis, and exogenous UC-MSCs may be useful for ITP therapy.

journal_name

Br J Haematol

authors

Li H,Guan Y,Sun B,Dou X,Liu X,Xue F,Fu R,Zhang L,Yang R

doi

10.1111/bjh.16953

subject

Has Abstract

pub_date

2020-07-16 00:00:00

eissn

0007-1048

issn

1365-2141

pub_type

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