Respiratory - Pulmonary Fibrosis

IDIOPATHIC PULMONARY FIBROSIS

Mast cells with their pivotal role in tissue repair and remodeling are crucially involved in the pathogenesis of fibrotic diseases, such as idiopathic pulmonary fibrosis, cardiac fibrosis and renal fibrosis, with often high morbidity rate.

In patients with pulmonary fibrosis the mast cell density is significantly increased (up to 10 times higher than in normal patients) correlating with the degree of fibrosis, lung function and clinical disease progression. These chronically activated mast cells release fibrogenic mediators, such as histamine, renin, TGF-β, IL-4, IL-6, IL-13, IL-21, tryptase CTGF, ATII, VEGF, PDGF, GMCSF, CCL2, CCL5 and more that contribute to the disease progression. Drugs known to partially inhibit mast cell activity have demonstrated first promising anti-fibrotic effects in in-vitro and in-vivo preclinical models of fibrosis. There is an urgent need for new therapies that selectively inhibit mast cell activity and reduce the mast cell burden.

Idiopathic Pulmonary Fibrosis is a rare disease that affects an estimated 450.000 patients globally.

Scientific Sources
  1. Shimbori C., Upagupta C., Forsythe P., Kolb M.: The role of mast cells in the pathophysiology of pulmonary fibrosis. In: Willis M., Yates C., Schisler J. (eds) Fibrosis in Disease. Molecular and Translational Medicine. Humana Press, Cham, 2019
  2. Catherine Overed-Sayer, Laura Rapley,Tomas Mustelin and Deborah L. Clarke, are mast cells instrumental for fibrotic diseases, frontiers in pharmacology, January 2014, Volume 4, Article 174, 1
  3. Arul Veerappan, Nathan J. O’Connor et al, Mast Cells: A pivotal role in pulmonary fibrosis, DNA and cell biology, Volume 32, Number 4, 2013
  4. Hügle T, Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly. 2014 Sep 3; 144: w13999.