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E3 ubiquitin ligase casitas B-lineage lymphoma-b modulates T-cell anergic resistance via phosphoinositide 3-kinase signaling in patients with immune thrombocytopenia.
Liu, Lu; Xiang, Yujiao; Shao, Linlin; Yuan, Chenglu; Song, Xiaofeng; Sun, Meng; Liu, Yanfeng; Zhang, Xianlei; Du, Shenghong; Hou, Ming; Peng, Jun; Shi, Yan.
Afiliación
  • Liu L; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of Hematology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, Shandong, China.
  • Xiang Y; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Shao L; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • Yuan C; Department of Hematology, Qilu Hospital (Qingdao) of Shandong University, Qingdao, Shandong, China.
  • Song X; Department of Hand and Foot Surgery, Qilu Hospital (Qingdao) of Shandong University, Qingdao, Shandong, China.
  • Sun M; Jinan Vocational College of Nursing, Jinan, Shandong, China.
  • Liu Y; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • Zhang X; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • Du S; Department of Hematology, Taian Central Hospital, Taian, Shandong, China.
  • Hou M; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Clinical Research Center in Hematological Diseases, Jinan, Shandong, China
  • Peng J; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
  • Shi Y; Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China. Electronic address: shiyansjj@163.com.
J Thromb Haemost ; 22(4): 1202-1214, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38184203
ABSTRACT

BACKGROUND:

The E3 ubiquitin ligase casitas B-lineage lymphoma-b (CBLB) is a newly identified component of the ubiquitin-dependent protein degradation system and is considered an important negative regulator of immune cells. CBLB is essential for establishing a threshold of T-cell activation and regulating peripheral T-cell tolerance through various mechanisms. However, the involvement of CBLB in the pathogenesis of immune thrombocytopenia (ITP) is unknown.

OBJECTIVES:

We aimed to investigate the expression and role of CBLB in CD4+ T cells obtained from patients with ITP through quantitative proteomics analyses.

METHODS:

CD4+ T cells were transfected with adenoviral vectors overexpressing CBLB to clarify the effect of CBLB on anergic induction of T cells in patients with ITP. DNA methylation levels of the CBLB promoter and 5' untranslated region (UTR) in patient-derived CD4+ T cells were detected via MassARRAY EpiTYPER assay (Agena Bioscience).

RESULTS:

CD4+ T cells from patients with ITP showed resistance to anergic induction, highly activated phosphoinositide 3-kinase-protein kinase B (AKT) signaling, decreased CBLB expression, and 5' UTR hypermethylation of CBLB. CBLB overexpression in T cells effectively attenuated the elevated phosphorylated protein kinase B level and resistance to anergy. Low-dose decitabine treatment led to significantly elevated levels of CBLB expression in CD4+ T cells from 7 patients showing a partial or complete response.

CONCLUSION:

These results indicate that the 5' UTR hypermethylation of CBLB in CD4+ T cells induces resistance to T-cell anergy in ITP. Thus, the upregulation of CBLB expression by low-dose decitabine treatment may represent a potential therapeutic approach to ITP.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Púrpura Trombocitopénica Idiopática / Linfoma Límite: Humans Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Púrpura Trombocitopénica Idiopática / Linfoma Límite: Humans Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido