Document Detail


Critical role for IL-17A/F in the immunopathogenesis of obliterative airway disease induced by Anti-MHC I antibodies.
MedLine Citation:
PMID:  23325004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Haseeb Ilias Basha; Sabarinathan Ramachandran; Venkataswarup Tiriveedhi; Masashi Takenaka; Vijay Subramanian; Dilip S Nath; Nicholas Benshoff; G Alec Patterson; Thalachallour Mohanakumar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  95     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-03-07     Revised Date:  2014-01-28    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  293-300     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / administration & dosage
Antibodies, Neutralizing / administration & dosage
Antigens, CD11b / metabolism
Autoantibodies / immunology*
Autoimmunity*
Biological Markers / metabolism
Bronchioles / immunology*,  pathology
Bronchiolitis Obliterans / genetics,  immunology*,  pathology,  prevention & control
Collagen Type V / immunology
Disease Models, Animal
Forkhead Transcription Factors / metabolism
Histocompatibility Antigens Class I / immunology*
Inflammation Mediators / metabolism*
Interleukin-17 / deficiency,  genetics,  metabolism*
Interleukin-2 Receptor alpha Subunit / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pulmonary Fibrosis / immunology,  pathology,  prevention & control
Signal Transduction
Th17 Cells / immunology*
Time Factors
Tubulin / immunology
Grant Support
ID/Acronym/Agency:
HL092514/HL/NHLBI NIH HHS; R01 HL092514/HL/NHLBI NIH HHS; T32 HL007776/HL/NHLBI NIH HHS; T32 HL07776/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Neutralizing; 0/Antigens, CD11b; 0/Autoantibodies; 0/Biological Markers; 0/Collagen Type V; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Histocompatibility Antigens Class I; 0/Il17a protein, mouse; 0/Il17f protein, mouse; 0/Il2ra protein, mouse; 0/Inflammation Mediators; 0/Interleukin-17; 0/Interleukin-2 Receptor alpha Subunit; 0/Tubulin
Comments/Corrections

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