Role of complement activation in obliterative bronchiolitis post-lung transplantation.

Published

Journal Article

Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.

Full Text

Duke Authors

Cited Authors

  • Suzuki, H; Lasbury, ME; Fan, L; Vittal, R; Mickler, EA; Benson, HL; Shilling, R; Wu, Q; Weber, DJ; Wagner, SR; Lasaro, M; Devore, D; Wang, Y; Sandusky, GE; Lipking, K; Pandya, P; Reynolds, J; Love, R; Wozniak, T; Gu, H; Brown, KM; Wilkes, DS

Published Date

  • October 2013

Published In

Volume / Issue

  • 191 / 8

Start / End Page

  • 4431 - 4439

PubMed ID

  • 24043901

Pubmed Central ID

  • 24043901

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1202242

Language

  • eng