title: Critical role for IL-17A/F in the immunopathogenesis of obliterative airway disease induced by Anti-MHC I antibodies.
abstract: BACKGROUND
  The IL-17 axis is implicated in pathogenesis of chronic rejection after human lung transplantation. Using a murine model of obliterative airway disease (OAD), we recently demonstrated that Abs to MHC class I antigens can induce immune responses to self-antigens that contributes to immunopathogenesis of chronic rejection. Using a murine model of OAD, we determined the role of IL-17 family members in induction of autoimmunity leading to OAD after ligation of MHC class I.
  
  
  METHODS
  Anti-MHC class I or control antibodies (Abs) were administered intrabronchially to wild-type (WT) and IL-17a knock out (IL-17A-/-) C57BL/6.
  
  
  RESULTS
  By day 30, anti-MHC I administered endobronchially in IL-17A-/- mice demonstrated significant reduction in cellular infiltration, a 36.8% reduction in CD4 T cells, 62.7% in CD11b macrophages, 37.5% in degree of fibrosis, 1.94 fold and 2.17 fold decrease in anti-KAT and anti-Col-V, respectively, when compared with wild-type mice. Analysis of lung infiltrating cells in anti-MHC I WT revealed increase in IL-17A (KAT:92+21,Col-V:103+19spm) and IL-17F (KAT:5.03%,Col-V:2.75%) secreting CD4+ T cells. However, administration of anti-MHC I in IL-17A-/- demonstrated increase only in IL-17F for KAT (13.70%) and Col-V (7.08%). Anti-IL-17(A-F) mAb administration after anti-MHC I abrogated OAD in both WT and IL-17A-/-.
  
  
  CONCLUSIONS
  Our findings indicate that IL-17A and IL-17F secreted by CD4+Th17 cells specific to lung self-antigens are critical mediators of autoimmunity leading to the pathogenesis of OAD.
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Haseeb Ilias
authors: HI
authors: Basha
authors: Sabarinathan
authors: S
authors: Ramachandran
authors: Venkataswarup
authors: V
authors: Tiriveedhi
authors: Masashi
authors: M
authors: Takenaka
authors: Vijay
authors: V
authors: Subramanian
authors: Dilip S
authors: DS
authors: Nath
authors: Nicholas
authors: N
authors: Benshoff
authors: G Alec
authors: GA
authors: Patterson
authors: Thalachallour
authors: T
authors: Mohanakumar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D055745:Bronchioles / Q000276:immunology* / Q000473:pathology; D001989:Bronchiolitis Obliterans / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D039481:CD11b Antigen / Q000378:metabolism; D024062:Collagen Type V / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*; D013997:Time Factors; D014404:Tubulin / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D015415:Biomarkers; D039481:CD11b Antigen; D024062:Collagen Type V; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015395:Histocompatibility Antigens Class I; C098680:Il17a protein, mouse; C515932:Il17f protein, mouse; C508018:Il2ra protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D014404:Tubulin