Collagen type V (Col(V))

Collagen type V is a minor fibrillar collagen that is normally sequestered within the larger Type I collagen fibrils of the lung's extracellular matrix (Wilkes et al., 2011, American Journal of Respiratory and Critical Care Medicine). Under conditions of chronic lung injury, such as idiopathic pulmonary fibrosis (IPF), the degradation of the matrix exposes Collagen type V to the immune system, triggering a pathological autoimmune response (Vittal et al., 2013, American Journal of Physiology-Lung Cellular and Molecular Physiology). This response involves the production of anti-Col(V) antibodies and the activation of Col(V)-specific Th1 cells, which correlate with disease severity and lung function decline (Wilkes et al., 2011). As a therapeutic target, Collagen type V is approached through the induction of mucosal tolerance, where oral administration of the protein aims to suppress the harmful immune response (Burlingham et al., 2007, Journal of Clinical Investigation). The investigational drug IW001 is an oral bovine Collagen type V formulation that has been evaluated in clinical trials for its ability to slow the progression of IPF by downregulating this autoimmunity (ClinicalTrials.gov, NCT01181258). Beyond IPF, this autoimmune mechanism is also heavily implicated in the pathogenesis of bronchiolitis obliterans syndrome following lung transplantation (Hachem et al., 2010, Journal of Heart and Lung Transplantation). Targeting this response represents a novel immunomodulatory strategy in fibrotic lung disease, distinct from traditional anti-fibrotic or immunosuppressive therapies.

Other names

COL5A1COL5A2COL5A3Collagen alpha-1(V) chainCollagen alpha-2(V) chainCollagen alpha-3(V) chain

Induction of oral tolerance to suppress the autoimmune response against endogenous Type V collagen.