[Frontiers in Bioscience 17, 2306-2326, June 1, 2012]

IL-6, IL-17 and STAT3: a holy trinity in auto-immunity?

Annalisa Camporeale1, Valeria Poli1

1Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy


1. Abstract
2. Introduction
2.1. IL-6 in the development of auto-immunity
2.1.1. IL-6 and Rheumatoid Arthritis
2.1.2. IL-6 and Multiple Sclerosis
2.1.3. IL-6 and Myocarditis
3. The discovery of Th17 cells shed light on the role of IL-6 in auto-immune diseases.
4. STAT3 enters the game
5. IL-6, IL-17 and STAT3: the holy trinity in auto-immunity?
6. The IL-6-IL-17-STAT3 loop in inflammation-driven tumourigenesis
7. Conclusions
8. Acknowledgments
9. References


Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of the cross talk between haematopoietic/immune cells and stromal cells, including the onset and resolution of inflammation, responses to infection, tissue remodelling and cancer. It is produced, among others, by fibroblasts, endothelial cells, macrophages and lymphocytes. IL-6 can interact with both membrane-bound and soluble forms of its ligand-binding receptor, the IL-6Ralpha, triggering signalling via dimerization of gp130, the signalling subunit of the IL-6 receptor complex. This leads to the activation of the JAK/STAT pathway and mainly culminates in the activation of the STAT3 transcription factor. Both IL-6 and STAT3 have recently emerged as main regulators of the differentiation and function of Th17 cells, via a positive feedback loop enhancing expression and/or activation of IL-6 itself, IL-17 and STAT3. Dysregulated IL-6 production and signalling are associated with chronic inflammatory diseases, auto-immunity and cancer, and are the object of intense translational research as promising therapeutic targets.