HIF-1α induced by hypoxic condition regulates Treg/Th17 axis polarization in chronic immune thrombocytopenia

Hao Gu; Zhifa Wang; Xingjuan Xie; Hui Chen; Juntao Ouyang; Runhui Wu; Zhenping Chen

doi:10.1016/j.intimp.2024.111810

HIF-1α induced by hypoxic condition regulates Treg/Th17 axis polarization in chronic immune thrombocytopenia

Int Immunopharmacol. 2024 Apr 20:131:111810. doi: 10.1016/j.intimp.2024.111810. Epub 2024 Mar 15.

Authors

Hao Gu¹, Zhifa Wang², Xingjuan Xie³, Hui Chen³, Juntao Ouyang³, Runhui Wu⁴, Zhenping Chen⁵

Affiliations

¹ Hematologic Disease Laboratory, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045.
² Hematologic Disease Laboratory, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045; Department of Hematology, Beijing Key Laboratory of Pediatric Hematology-Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045.
³ Hematologic Disease Laboratory, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045.
⁴ Department of Hematology, Beijing Key Laboratory of Pediatric Hematology-Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045. Electronic address: runhuiwu@hotmail.com.
⁵ Hematologic Disease Laboratory, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China 100045. Electronic address: chenzhenping@outlook.com.

PMID: 38492341
DOI: 10.1016/j.intimp.2024.111810

Abstract

Immune thrombocytopenia (ITP) is an acquired immune disorder characterized by increased platelet destruction and reduced platelet (Plt) production. Hypoxia-inducible factor-1α (HIF-1α) have regulatory effects on Treg/Th17 axis balance and may represent relevant factors in the pathogenesis of ITP. Treg/Th17 ratio, serum levels and gene expression were investigated in new diagnosed ITP (NITP) and chronic ITP (CITP). The Treg/Th17 ratio obviously decreased in CITP (P = 0.001). The ratio of Treg/Th17 was correlated with the level of HIF-1α level both in mRNA (r = 0.49, P < 0.0001) and serum level (r = 0.50, P < 0.0001). However, none statistical upregulation of HIF-1α was observed in CITP. In vitro, There was significant polarization difference of Treg/Th17 axis (P = 0.042) and Foxp3-MFI/IL17-MFI (P = 0.0003) in hypoxic condition between NITP and CITP. These findings suggest that HIF-1α induced by hypoxia plays a crucial role in the chronicity of ITP by mediating the imbalance of the Treg/Th17 axis.

Keywords: Hypoxia-inducible factor-1α (HIF-1α); ITP; Pediatrics; Treg/Th17 ratio.

MeSH terms

Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism
Humans
Nitroimidazoles*
Purpura, Thrombocytopenic, Idiopathic*
T-Lymphocytes, Regulatory
Th17 Cells
Theophylline / analogs & derivatives*
Thrombocytopenia*

Substances

7-(4'-(2-nitroimidazole-1-yl)butyl)theophylline
Forkhead Transcription Factors
Nitroimidazoles
Theophylline