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Updated: Jan 25, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Interleukin-17 pathways in systemic sclerosis-associated fibrosis
Sakir Ahmed1, Durga Prasanna Misra2, Vikas Agarwal3
1Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences (KIMS), KIIT University, Bhubaneswar, 751024, India.
Abstract:
Fibrosis is unregulated tissue repair that may cause impairment of organ function, especially in end-organ damage. Systemic sclerosis (SSc) is the prototype systemic fibrosing disorder. Classical targets for fibrosis in SSc like transforming growth factor Beta (TGF-β), Interleukin-6 (IL-6), and multiple tyrosine kinases, have not yielded therapeutic benefit. There is multitude of evidence from across different tissues like the heart, lung, skin, liver, colon, and, to some extent, the kidney, that interleukin-17 (IL-17) and its downstream pathways are strongly associated with the initiation and propagation of fibrosis. Data from scleroderma patients, as well as from animal models of SSc, mirror these findings. Interestingly, hitherto unknown to be related to IL-17, newer molecules like Programmed Death-protein1 (PD-1), the phosphatase SHP2, along with known signal transducers like signal transducer and activator of transcription (STAT3), have been recently shown to be involved in the pathogenesis of fibrosis. Related molecules include the intracellular signalling molecules Ras/Erk, mammalian target organ of rapamycin (mTOR), and complement components. The biology of these pathways has not yet been fully elucidated to predict regulatory mechanisms, redundancies, and potential off-target effects. All these need to be better understood in the context of each other, in an effort to arrive at the optimal target to modulate fibrosis.
Insights
Fibrosis, a key feature of systemic sclerosis (SSc), involves complex pathways. Understanding novel targets like Interleukin-17 (IL-17) and its related molecules is crucial for developing effective antifibrotic therapies.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- Fibrosis, characterized by unregulated tissue repair, impairs organ function and is central to systemic sclerosis (SSc).
- Previous therapeutic targets for SSc, including TGF-β and IL-6, have shown limited success.
- Emerging evidence links Interleukin-17 (IL-17) and its downstream pathways to fibrosis across multiple organs.
Purpose of the Study:
- To review the current understanding of fibrotic mechanisms in SSc.
- To highlight the role of IL-17 and newly identified signaling molecules in fibrosis.
- To emphasize the need for further research into these pathways for therapeutic development.
Main Methods:
- Literature review of studies on fibrosis, SSc, and related molecular pathways.
- Analysis of evidence linking IL-17, PD-1, SHP2, STAT3, Ras/Erk, mTOR, and complement components to fibrotic processes.
- Synthesis of data from patient cohorts and animal models of SSc.
Main Results:
- IL-17 and its downstream effectors are strongly implicated in the initiation and progression of fibrosis in SSc.
- Novel molecules such as Programmed Death-protein1 (PD-1) and SHP2, alongside STAT3, Ras/Erk, mTOR, and complement, are involved in fibrotic pathogenesis.
- These pathways exhibit complex interactions, redundancies, and potential for off-target effects.
Conclusions:
- IL-17 and associated molecular pathways represent promising targets for antifibrotic therapies in SSc.
- A comprehensive understanding of the interplay between these newly identified molecules and IL-17 is essential.
- Further elucidation of these complex biological networks is required to optimize therapeutic strategies for modulating fibrosis.
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