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Homeobox Transcription Factor HOXB4 Distinctly Modulates Th2 and Th9 Cell Differentiation
Shagnik Chattopadhyay1, Sayantee Hazra1, Biswajit Biswas1
1Department of Bioscience and Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, India.
European Journal of Immunology
|July 21, 2025
Summary
The homeobox transcription factor HOXB4 regulates T helper cell differentiation. HOXB4, induced by TGF-β, influences Th9 and Th2 cells by interacting with PU.1 and binding regulatory DNA regions.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD4+ T helper cells are crucial for immunity and tolerance.
- Their differentiation into subsets is regulated by transcription factors, cytokines, and epigenetic factors.
Purpose of the Study:
- To elucidate the molecular mechanisms of HOXB4 in Th2 and Th9 cell differentiation.
- To investigate the relationship between HOXB4, TGF-β signaling, and T helper cell subsets.
Main Methods:
- Investigated HOXB4 induction in T helper cells.
- Analyzed cytokine secretion (IL-9, IL-10, IL-4, IL-13) in Th2 and Th9 cells.
- Performed promoter activity assays and transcription factor interaction studies (HOXB4, PU.1, GATA3).
Main Results:
- HOXB4 induction was dependent on TGF-β.
- HOXB4 overexpression enhanced IL-9 secretion in Th9 cells and IL-10 in Th2 cells.
- HOXB4 transactivated Il9 and Il10 promoters, interacted with PU.1, and bound PU.1 response elements.
Conclusions:
- HOXB4 acts downstream of TGF-β signaling.
- HOXB4 distinctly regulates Th2 and Th9 cell differentiation through PU.1 interaction and DNA binding.
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