Critical role for IL-17A/F in the Immunopathogenesis of Obliterative airway disease induced by anti-mhc i antibodies

Haseeb Ilias Basha, Sabarinathan Ramachandran, Venkataswarup Tiriveedhi, Masashi Takenaka, Vijay Subramanian, Dilip S. Nath, Nicholas Benshoff, G. Alec Patterson, Thalachallour Mohanakumar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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-/-. 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.

Original languageEnglish (US)
Pages (from-to)293-300
Number of pages8
JournalTransplantation
Volume95
Issue number2
DOIs
StatePublished - Jan 27 2013

Keywords

  • Anti-MHC
  • Autoimmunity.
  • IL-17

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