title: Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP).
abstract: Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.
authors: Department of Hematology, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, China, yaorongxin@126.com.
authors: Rongxin
authors: R
authors: Yao
authors: Ying
authors: Y
authors: Lin
authors: Qianqian
authors: Q
authors: Li
authors: Xieming
authors: X
authors: Zhou
authors: Xiahui
authors: X
authors: Pan
authors: Yunhua
authors: Y
authors: Bao
authors: Muqing
authors: M
authors: He
authors: Baoling
authors: B
authors: Zhu
authors: Wenjian
authors: W
authors: Guo
authors: Xiaoji
authors: X
authors: Lin
authors: Limin
authors: L
authors: Jin
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D050990:GATA3 Transcription Factor / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508611:IL11 protein, human; D017370:Interleukin-11; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor