Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia.
Thalidomide (THD) is an immunomodulatory agent used to treat immune-mediated diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder in which impaired mesenchymal stem cells (MSCs) are potentially involved. We demonstrated that MSCs in ITP patients had reduced proliferative capacity and lost their immunosuppressive function, which could be corrected with THD treatment. According to the gene profile, the downregulation of caspase-8 and caspase-10, and upregulation of oct3/4 and tgf-β1, may be associated with THD modulation. Dendritic cells (DCs) played an important role in mediating the inhibitory activity of MSCs. To study the functional alteration of DCs elicited by MSCs, we sorted DCs after incubation with MSCs and performed T-lymphocyte reaction assays. The THD-modulated MSCs from ITP patients induced mature DCs to become tolerogenic DCs, whereas unmodulated MSCs had no effect. The induction of tolerogenicity in DCs by MSCs was dependent on the expression of TIEG1 in DCs. The study reveals the inability of MSCs from ITP patients to induce tolerogenic ability in DCs. THD could restore the regulatory effect of MSCs on DCs. These findings will help us understand the pathogenesis of ITP, and with appropriate safeguards, THD may benefit patients with ITP.
Department of Hematology, Qilu Hospital, and.
Ji
J
Ma
Yun-Na
YN
Ning
Miao
M
Xu
Yu
Y
Hou
Ning
N
Wang
Xiao-Yan
XY
Hou
Ying-Yi
YY
Yu
Hui
H
Li
Wei-Dong
WD
He
Lin-Lin
LL
Shao
Hai
H
Zhou
Ya-Nan
YN
Min
Xin-Guang
XG
Liu
Yan
Y
Shi
Ping
P
Qin
Cheng-Shan
CS
Guo
Ming
M
Hou
Jun
J
Peng
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D034622:RNA Interference; D013792:Thalidomide / Q000494:pharmacology*; D055815:Young Adult
D051765:Early Growth Response Transcription Factors; D007166:Immunosuppressive Agents; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D013792:Thalidomide