Role of complement activation in obliterative bronchiolitis post-lung transplantation

J Immunol. 2013 Oct 15;191(8):4431-9. doi: 10.4049/jimmunol.1202242. Epub 2013 Sep 16.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmunity
  • Bronchiolitis Obliterans / immunology*
  • Bronchoalveolar Lavage Fluid
  • CD55 Antigens / biosynthesis
  • Collagen Type V / immunology
  • Complement Activation*
  • Complement C3a / biosynthesis
  • Complement C5
  • Down-Regulation
  • Graft Rejection / immunology*
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-6 / biosynthesis
  • Lung Transplantation / adverse effects*
  • Lymphocyte Culture Test, Mixed
  • Membrane Cofactor Protein / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Complement / biosynthesis
  • Receptors, Complement 3b


  • CD55 Antigens
  • Collagen Type V
  • Complement C5
  • Cr1l protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Membrane Cofactor Protein
  • Receptors, Complement
  • Receptors, Complement 3b
  • Complement C3a