The TWEAK/Fn14/CD163 axis-implications for metabolic disease.
Wiktoria Ratajczak1, Sarah D Atkinson1, Catriona Kelly2
1Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital Campus, C-TRIC Building Glenshane Road, Derry/Londonderry, Northern Ireland, UK.
Reviews in Endocrine & Metabolic Disorders
|September 20, 2021
Summary
The TWEAK/Fn14/CD163 axis regulates immune signaling and impacts metabolic diseases. While protective in healthy tissues, this pathway becomes detrimental in chronic inflammation, affecting cardiovascular health.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a TNF superfamily member regulating cellular events like proliferation, migration, and inflammation.
- TWEAK signaling involves pathways such as NF-κB, ERK/MAPK, Notch, EGFR, and AP-1.
- Two TWEAK receptors, Fn14 and CD163, mediate distinct cellular responses based on TWEAK form and binding context.
Purpose of the Study:
- To review the current understanding of the TWEAK/Fn14/CD163 axis.
- To elucidate the role of this axis in immune signaling and metabolic disease.
- To highlight the dual role of TWEAK signaling in health and disease.
Main Methods:
- Literature review of TWEAK/Fn14/CD163 axis functions.
- Analysis of TWEAK's involvement in various signaling pathways.
- Examination of TWEAK's role in different disease contexts.
Main Results:
- TWEAK signaling is context-dependent, varying with receptor, tissue, and cytokine milieu.
- The TWEAK/Fn14/CD163 axis is implicated in metabolic diseases, autoimmune disorders, and ischemic stroke.
- Low soluble TWEAK levels predict adverse cardiovascular outcomes, particularly in diabetic patients.
Conclusions:
- The TWEAK/Fn14/CD163 axis is a key regulator of immune responses.
- TWEAK signaling shifts from protective to detrimental in chronic inflammatory conditions.
- Understanding this axis is crucial for metabolic and cardiovascular disease progression.
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