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Role of bone marrow‐derived mesenchymal stem cell defects in CD8 + CD28 – suppressor T‐lymphocyte induction in patients with immune thrombocytopenia and associated mechanisms
Author(s) -
Li Huiyuan,
Guan Yue,
Sun Boyang,
Dou Xueqing,
Liu Xiaofan,
Xue Feng,
Fu Rongfeng,
Zhang Lei,
Yang Renchi
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16953
Subject(s) - mesenchymal stem cell , bone marrow , immune system , cancer research , cd8 , immunology , cell , cell therapy , t cell , cd28 , stem cell , medicine , chemistry , biology , microbiology and biotechnology , biochemistry
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.