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-/-. CONCLUSION: 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.
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-/-. CONCLUSION: 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: A Jaramillo; M A Smith; D Phelan; S Sundaresan; E Trulock; J Lynch; J Cooper; G A Patterson; T Mohanakumar Journal: Transplant Proc Date: 1999 Feb-Mar Impact factor: 1.066
Authors: A Jaramillo; M A Smith; D Phelan; S Sundaresan; E P Trulock; J P Lynch; J D Cooper; G A Patterson; T Mohanakumar Journal: Transplantation Date: 1999-04-27 Impact factor: 4.939
Authors: S Sundaresan; T Mohanakumar; M A Smith; E P Trulock; J Lynch; D Phelan; J D Cooper; G A Patterson Journal: Transplantation Date: 1998-03-15 Impact factor: 4.939
Authors: Kim C Lu; Andrés Jaramillo; Eric N Mendeloff; Charles B Huddleston; Stuart C Sweet; G Alexander Patterson; T Mohanakumar Journal: J Heart Lung Transplant Date: 2003-01 Impact factor: 10.247
Authors: William J Burlingham; Robert B Love; Ewa Jankowska-Gan; Lynn D Haynes; Qingyong Xu; Joseph L Bobadilla; Keith C Meyer; Mary S Hayney; Ruedi K Braun; Daniel S Greenspan; Bagavathi Gopalakrishnan; Junchao Cai; David D Brand; Shigetoshi Yoshida; Oscar W Cummings; David S Wilkes Journal: J Clin Invest Date: 2007-11 Impact factor: 14.808
Authors: Walker Julliard; John H Fechner; Leah Owens; Chelsea A O'Driscoll; Ling Zhou; Jeremy A Sullivan; Lynn Frydrych; Amanda Mueller; Joshua D Mezrich Journal: Transplant Direct Date: 2017-04-25