Fibrosis and Immune Dysregulation in Systemic Sclerosis

  • Yahya Argobi
  • Gideon P. Smith
Part of the Molecular and Translational Medicine book series (MOLEMED)


Systemic sclerosis is a rare connective tissue disease of unclear etiology characterized by cutaneous and internal organ sclerosis. It has a complex pathogenesis believed to include vascular abnormalities with accompanying autoimmunity leading to tissue sclerosis. This chapter summarizes the current knowledge about systemic sclerosis pathogenesis and reviews the role of immune imbalance and its relationship with vascular damage and sustained sclerosis. Systemic sclerosis is unlike other connective tissue diseases in that immunosuppressive drugs alone are usually insufficient to control the disease and developing treatments for the other aspects, i.e., vasculopathy and fibrosis, is paramount in systemic sclerosis. Over the past decade, studies on animals and humans have revealed valuable information about systemic sclerosis molecular mechanisms. In addition, there have been a number of clinical trials targeting specific cytokines and signaling pathways involved in systemic sclerosis that have helped eliminate potential therapeutic pathways from consideration. Combining the findings from these disparate studies should help narrow the search for novel therapies.


Systemic sclerosis Scleroderma Sclerosis Fibrosis Connective tissue 



Angiotensin-converting enzyme inhibitor


Transcription factor activator protein-1


RNA polymerase III antibody


Angiotensin II type 1 receptor




B-cell-activating factor




Chronic graft-versus-host disease


Type III collagen


Connective tissue growth factor


T lymphocyte-associated antigen 4


Damage-associated molecular patterns


Extracellular matrix




Endothelin-1 type A receptor


Friend leukemia integration 1




Fos-related antigen-2




Interstitial lung disease


Idiopathic pulmonary fibrosis


Janus kinases


Kruppel-like factor 5


Lysophosphatidic acid




Modified Rodnan skin score


Plasminogen activator inhibitor-1


Platelet-derived growth factor


Platelet-derived growth factor receptor


Peroxisome proliferator-activated receptor gamma


Reactive oxygen species


Raynaud’s phenomenon


Retinoid X receptor


Topoisomerase 1


Smooth muscle actin


Systemic sclerosis


Transducers and activators of transcription


Transforming growth factor-B


T helper cell


Toll-like receptors


Tumor necrosis factor


Regulatory T cell


Tight skin 1


Tight skin 2


Urokinase-type plasminogen activator receptor


Vascular cell adhesion molecule-1


Vascular endothelial growth factor


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yahya Argobi
    • 1
  • Gideon P. Smith
    • 2
  1. 1.King Khalid UniversityAbhaSaudi Arabia
  2. 2.Department of DermatologyMGHBostonUSA

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