PMID- 23926306 OWN - NLM STAT- MEDLINE DCOM- 20131115 LR - 20210202 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 122 IP - 12 DP - 2013 Sep 19 TI - Thalidomide corrects impaired mesenchymal stem cell function in inducing tolerogenic DCs in patients with immune thrombocytopenia. PG - 2074-82 LID - 10.1182/blood-2013-03-491555 [doi] AB - 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-beta1, 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. FAU - Ma, Ji AU - Ma J AD - Department of Hematology, Qilu Hospital, and. FAU - Ning, Yun-Na AU - Ning YN FAU - Xu, Miao AU - Xu M FAU - Hou, Yu AU - Hou Y FAU - Wang, Ning AU - Wang N FAU - Hou, Xiao-Yan AU - Hou XY FAU - Yu, Ying-Yi AU - Yu YY FAU - Li, Hui AU - Li H FAU - He, Wei-Dong AU - He WD FAU - Shao, Lin-Lin AU - Shao LL FAU - Zhou, Hai AU - Zhou H FAU - Min, Ya-Nan AU - Min YN FAU - Liu, Xin-Guang AU - Liu XG FAU - Shi, Yan AU - Shi Y FAU - Qin, Ping AU - Qin P FAU - Guo, Cheng-Shan AU - Guo CS FAU - Hou, Ming AU - Hou M FAU - Peng, Jun AU - Peng J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130807 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Early Growth Response Transcription Factors) RN - 0 (Immunosuppressive Agents) RN - 0 (KLF10 protein, human) RN - 0 (Kruppel-Like Transcription Factors) RN - 4Z8R6ORS6L (Thalidomide) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Case-Control Studies MH - Cell Proliferation/drug effects MH - Dendritic Cells/*immunology MH - Early Growth Response Transcription Factors/genetics/metabolism MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Humans MH - Immune Tolerance/*drug effects MH - Immunosuppressive Agents/*pharmacology MH - Kruppel-Like Transcription Factors/genetics/metabolism MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Middle Aged MH - Purpura, Thrombocytopenic, Idiopathic/genetics/*immunology/*metabolism MH - RNA Interference MH - Thalidomide/*pharmacology MH - Young Adult EDAT- 2013/08/09 06:00 MHDA- 2013/11/16 06:00 CRDT- 2013/08/09 06:00 PHST- 2013/08/09 06:00 [entrez] PHST- 2013/08/09 06:00 [pubmed] PHST- 2013/11/16 06:00 [medline] AID - S0006-4971(20)43146-5 [pii] AID - 10.1182/blood-2013-03-491555 [doi] PST - ppublish SO - Blood. 2013 Sep 19;122(12):2074-82. doi: 10.1182/blood-2013-03-491555. Epub 2013 Aug 7.