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Novel insights into the dynamic function of PRC2 in innate immunity
Rosalie W M Kempkes1, Rab K Prinjha2, Menno P J de Winther1
1Amsterdam UMC location University of Amsterdam, Department of Medical Biochemistry, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Disease, Amsterdam, the Netherlands.
Polycomb repressive complex 2 (PRC2) regulates cell identity and innate immunity. Inhibiting PRC2, particularly EZH2, shows promise in reducing inflammation and disease severity.
Area of Science:
- Epigenetics
- Immunology
- Molecular Biology
Background:
- Polycomb repressive complex 2 (PRC2) is crucial for maintaining cell identity through histone methylation (H3K27me3).
- Emerging evidence highlights PRC2's role beyond cell differentiation, revealing significant immunomodulatory functions.
- The catalytic subunit EZH2 is implicated in various inflammatory conditions.
Purpose of the Study:
- To explore the multifaceted roles of PRC2 in innate immunity, encompassing both canonical epigenetic and non-canonical regulatory mechanisms.
- To elucidate PRC2's influence on hematopoietic stem cell proliferation, myeloid differentiation, and overall innate immune response shaping.
- To underscore the therapeutic potential of targeting PRC2/EZH2 in inflammatory diseases.
Main Methods:
- Integration of data from diverse immunological research fields.
- Analysis of PRC2's epigenetic regulatory functions.
- Review of studies on PRC2 subunit involvement in innate immunity.
Main Results:
- PRC2 critically regulates hematopoietic stem cell proliferation and myeloid cell differentiation.
- PRC2 activity influences the development and function of innate immune cells.
- EZH2 upregulation correlates with inflammatory disease severity, and its inhibition ameliorates disease in mouse models.
Conclusions:
- PRC2 plays a significant role in innate immunity through both established and novel mechanisms.
- Targeting PRC2, especially EZH2, represents a promising therapeutic strategy for inflammatory diseases.
- Further research into PRC2's immunomodulatory functions can unlock new treatment avenues.
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