The TWEAK/Fn14/CD163 axis - Implications for metabolic disease

Wiktoria Ratajczak, SD Atkinson, Catriona Kelly

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)
52 Downloads (Pure)


TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression.
Original languageEnglish
JournalReviews in Endocrine and Metabolic Disorders
Early online date20 Sept 2021
Publication statusPublished online - 20 Sept 2021

Bibliographical note

Funding Information:
The authors’ work is supported by the European Union Regional Development Fund (ERDF) EU Sustainable Competitiveness Programme for N. Ireland, Northern Ireland Public Health Agency (HSC R&D) & Ulster University, and through a PhD scholarship to WR from the Department for the Economy, Northern Ireland.

Publisher Copyright:
© 2021, The Author(s).


  • Tweak
  • FN14
  • CD163
  • Diabetes
  • Cardiovascular Disease
  • Metabolic Disease


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