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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
PubMed

Insights

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.
Keywords:
CD163Cardiovascular DiseaseDiabetesFN14Metabolic DiseaseTWEAK

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