Abstract
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.
Highlights
Reports epitomized by studies of Janus activated kinase (Jak)-signal transducer and activator of transcription (STAT) cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signaldependent cytokine responses
Studies in animal models and cell systems have been aided by the widespread use of cytokine targeting therapies in patients with complex immune-mediated conditions, infectious diseases and cancer
This is epitomized by studies of the Jak-STAT pathway, which frequently combine methods common to the evaluation of cellular immunology, histology, functional genomics and the holistic analysis of the proteome and transcriptome
Summary
Making sense of IL-6 signalling cues in pathophysiology Millrine, David; Jenkins, Robert H.; Hughes, Stuart T. Citation for published version (APA): Millrine, D., Jenkins, R. Making sense of IL-6 signalling cues in pathophysiology. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim
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