Suzuki, HidemiLasbury, Mark E.Fan, LinVittal, RaginiMickler, Elizabeth A.Benson, Heather L.Shilling, RebeccaWu, QiangWeber, Daniel J.Wagner, Sarah R.Lasaro, MelissaDevore, DeniseWang, YiSandusky, George E.Lipking, KelseyPandya, PankitaReynolds, JohnLove, RobertWozniak, ThomasGu, HongmeiBrown, Krista M.Wilkes, David S.2015-10-292015-10-292013-10-15Suzuki, H., Lasbury, M. E., Fan, L., Vittal, R., Mickler, E. A., Benson, H. L., … Wilkes, D. S. (2013). Role of Complement Activation in Obliterative Bronchiolitis Post Lung Transplantation. Journal of Immunology (Baltimore, Md. : 1950), 191(8), 10.4049/jimmunol.1202242. http://doi.org/10.4049/jimmunol.12022420022-1767https://hdl.handle.net/1805/7298Obliterative 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 are unknown. The current study examines the role of complement activation in OB. Complement regulatory protein (CRP) (CD55, CD46, Crry/CD46) expression was down regulated in human and murine OB; and C3a, a marker of complement activation, was up regulated locally. IL-17 differentially suppressed Crry 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 down regulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed forward loop that may enhance CRP down regulation, suggesting that complement blockade could be a therapeutic strategy for OB.en-USPublisher Policylung transplantationcomplement activationobliterative bronchiolitischronic rejectionimmunologyArticle