Vittal, RaginiMickler, Elizabeth A.Fisher, Amanda J.Zhang, ChenRothhaar, KatiaGu, HongmeiBrown, Krista M.Emtiazdjoo, AmirLott, Jeremy M.Frye, Sarah B.Smith, Gerald N.Sandusky, George E.Cummings, Oscar W.Wilkes, David S.2025-04-282025-04-282013-10-21Vittal R, Mickler EA, Fisher AJ, et al. Type V collagen induced tolerance suppresses collagen deposition, TGF-β and associated transcripts in pulmonary fibrosis [published correction appears in PLoS One. 2018 Dec 6;13(12):e0209107. doi: 10.1371/journal.pone.0209107.]. PLoS One. 2013;8(10):e76451. Published 2013 Oct 21. doi:10.1371/journal.pone.0076451https://hdl.handle.net/1805/47502Rationale: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and matrix deposition. Recent reports highlight an autoimmune component in IPF pathogenesis. We have reported anti-col(V) immunity in IPF patients. The objective of our study was to determine the specificity of col(V) expression profile and anti-col(V) immunity relative to col(I) in clinical IPF and the efficacy of nebulized col(V) in pre-clinical IPF models. Methods: Col(V) and col(I) expression profile was analyzed in normal human and IPF tissues. C57-BL6 mice were intratracheally instilled with bleomycin (0.025 U) followed by col(V) nebulization at pre-/post-fibrotic stage and analyzed for systemic and local responses. Results: Compared to normal lungs, IPF lungs had higher protein and transcript expression of the alpha 1 chain of col(V) and col(I). Systemic anti-col(V) antibody concentrations, but not of anti-col(I), were higher in IPF patients. Nebulized col(V), but not col(I), prevented bleomycin-induced fibrosis, collagen deposition, and myofibroblast differentiation. Col(V) treatment suppressed systemic levels of anti-col(V) antibodies, IL-6 and TNF-α; and local Il-17a transcripts. Compared to controls, nebulized col(V)-induced tolerance abrogated antigen-specific proliferation in mediastinal lymphocytes and production of IL-17A, IL-6, TNF-α and IFN-γ. In a clinically relevant established fibrosis model, nebulized col(V) decreased collagen deposition. mRNA array revealed downregulation of genes specific to fibrosis (Tgf-β, Il-1β, Pdgfb), matrix (Acta2, Col1a2, Col3a1, Lox, Itgb1/6, Itga2/3) and members of the TGF-β superfamily (Tgfbr1/2, Smad2/3, Ltbp1, Serpine1, Nfkb/Sp1/Cebpb). Conclusions: Anti-col(V) immunity is pathogenic in IPF, and col(V)-induced tolerance abrogates bleomycin-induced fibrogenesis and down regulates TGF- β-related signaling pathways.en-USAttribution 4.0 InternationalIdiopathic pulmonary fibrosisAutoantibodiesBleomycinPulmonary fibrosisArticle