Rheumatology International

, Volume 39, Issue 7, pp 1135–1143 | Cite as

Interleukin-17 pathways in systemic sclerosis-associated fibrosis

  • Sakir Ahmed
  • Durga Prasanna Misra
  • Vikas AgarwalEmail author


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.


Interleukin 17 T helper 17 STAT3 Fibrosis Systemic sclerosis 



B-cell activating factor


Complement component 3a


Carbon tetrachloride


Chemokine ligand 5


Connective tissue growth factor


Epithelial-to-mesenchymal transition

ERK 1/2

Extracellular signal-regulated kinase 1/2


Fibroblast growth factor receptor 2

γδ T-cells

Gamma delta T cells


Granulocyte colony-stimulating factor


Growth/differentiation factor 15


Graft versus host disease




Immunoreceptor tyrosine-based inhibitory motifs


Mitogen-activated protein kinase


Matrix metalloproteinase-1


Messenger ribonucleic acid


Neutrophil extracellular traps


NOD-like receptor


NOD-like receptor (NLR) family pyrin containing domain 3


Nuclear factor kappa B


Programmed cell death 1


Receptor activator of nuclear factor kappa B ligand


Src homology 2


Systemic sclerosis


Signal transduction and activator of transcription-3


Transforming growth factor beta


T helper cell


Toll like receptor


Tumor necrosis factor alpha


T regulatory cell


Trichostatin A


Tight skin mouse 1


Author contributions

The conception and design of the study, acquisition of data, analysis and interpretation of data—SA, DPM, VA. Drafting the article—SA; Revising it critically for important intellectual content—DPM, VA. Final approval of the version to be submitted—SA, DPM, VA. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved—SA, DPM, VA.


No funding was received for this study.

Compliance with ethical standards

Conflict of interest

Sakir Ahmed declares that he has no conflict of interest, including no relationship with pharmaceutical companies. Durga Prasanna Misra declares that he has no conflict of interest, including no relationship with pharmaceutical companies. Vikas Agarwal declares that he has no conflict of interest, including no relationship with pharmaceutical companies.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences (KIMS)KIIT UniversityBhubaneswarIndia
  2. 2.Department of Clinical Immunology and RheumatologySanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)LucknowIndia

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