Making sense of IL-6 signalling cues in pathophysiology

David Millrine, Robert H. Jenkins, Stuart T. O. Hughes, Simon A. Jones (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)
49 Downloads (Pure)


Unravelling the molecular mechanisms that account for functional pleiotropy is a major challenge for researchers in cytokine biology. Cytokine–receptor cross-reactivity and shared signalling pathways are considered primary drivers of cytokine pleiotropy. However, reports epitomized by studies of Jak-STAT cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signal-dependent cytokine responses. Here, a regulatory interplay between STAT transcription factors and their convergence to specific genomic enhancers support the fine-tuning of cytokine responses controlling host immunity, functional identity, and tissue homeostasis and repair. In this review, we provide an overview of the signalling networks that shape the way cells sense and interpret cytokine cues. With an emphasis on the biology of interleukin-6, we highlight the importance of these mechanisms to both physiological processes and pathophysiological outcomes.

Original languageEnglish
Pages (from-to)567-588
Number of pages22
JournalFEBS Letters
Issue number5
Early online date7 Oct 2021
Publication statusE-pub ahead of print - 7 Oct 2021


  • Jak-STAT signalling
  • STAT transcription factors
  • arthritis
  • cytokine receptors
  • cytokines
  • epigenetics
  • inflammation
  • interleukin
  • microRNA
  • pathophysiology

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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