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Review
. 2019 Aug:120:282-288.
doi: 10.1016/j.cyto.2018.11.003. Epub 2019 Feb 14.

Interleukin-17: Friend or foe in organ fibrosis

Affiliations
Review

Interleukin-17: Friend or foe in organ fibrosis

Kritika Ramani et al. Cytokine. 2019 Aug.

Abstract

Fibrosis affects all vital organs accounting for a staggering 45% of deaths worldwide and no effective therapies are currently available. Unresolved inflammation triggers downstream signaling events that lead to organ fibrosis. In recent years, proinflammatory cytokine Interleukin-17 (IL-17) has been implicated in several chronic inflammatory diseases that often culminate in organ damage followed by impaired wound healing and fibrosis. In this review, we outline the contribution of the IL-17 in mediating fibrotic diseases in various organs. A comprehensive understanding of the inflammatory events, and particularly the details of IL-17 signaling in vivo, could be beneficial in designing new therapeutic or preventive approaches to treat fibrosis. Additionally, understanding organ-specific differences in IL-17 activity could lead to targeted therapies and help spare other organs from unwanted side effects.

Keywords: Fibrosis; IL-17; Inflammation.

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Figures

Fig 1:
Fig 1:. The immunology of organ fibrosis:
Cells respond to injury by secreting cytokines, chemokines and growth factors, setting the stage for inflammation that clears the insult and facilitate tissue repair and wound healing. In some cases chronic inflammation results in improper wound healing and initiates a cascade of profibrotic events in the organs. Chemokines recruit Th1, Th2 cells and Th17 and other IL-17 producing cells, as well as inflammatory monocytes. Th2 cytokines (IL-4, IL-5 and IL-13) convert monocytes to M2 macrophages. M2 macrophages are the major source of TGF-β and other growth factors required for trans-differentiation of tissue resident fibroblasts to ECM-secreting myofibroblasts. IFN-γ from Th1 cells converts monocytes to M1 macrophages. M1 macrophages inhibit myofibroblasts proliferation and facilitate the degradation of ECM proteins by producing matrix metalloproteinases (MMPs). Cytokines and growth factors secreted from tubular epithelial cells activate T cells, macrophages and myofibroblasts and aid in the process of ECM synthesis and deposition. The balance between ECM synthesis and degradation determines the outcome of the profibrotic cascade and eventually development of fibrosis. IL-17 produced from innate and adaptive IL-17 producing cells play both pro- or antifibrotic role depending on the organ affected and nature of initial insults.

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