Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation

V. Subramanian, S. Ramachandran, B. Banan, A. Bharat, X. Wang, N. Benshoff, D. Kreisel, A. E. Gelman, T. Mohanakumar

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Immune responses against lung-associated self-antigens (self-Ags) are hypothesized to play a role in the development of chronic lung graft rejection. We determined whether immune responses to lung self-Ags, K-alpha-1-tubulin (Kα1T) and Collagen V (Col-V) in the absence of alloimmunity, could promote airway inflammation and fibrosis. Following syngeneic murine orthotopic lung transplantation (LTx) we administered antibodies (Abs) to either Kα1T or Col-V or in combination to both of these self-Ags. As compared to recipients of isotype control Abs, Kα1T Abs and/or Col-V Abs-treated recipients had marked lung graft cellular infiltration and bronchiolar fibrosis. This inflammation was also associated the accumulation of Kα1T and Col-V-specific interferon-γ+ and IL-17+ T cells. Notably, the administration of Abs to Kα1T led to cellular and humoral immune responses to Col-V prior to development of fibrosis, and vice versa, indicating that epitope spreading can occur rapidly in an alloantigen independent manner. Collectively, these data support a model of chronic LTx rejection where the progressive loss of self-tolerance through epitope spreading promotes airway fibrosis. Strategies that target autoreactive Abs may be useful to inhibit chronic rejection of lung grafts.

Original languageEnglish (US)
Pages (from-to)2359-2366
Number of pages8
JournalAmerican Journal of Transplantation
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2014

Bibliographical note

Publisher Copyright:
© 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Keywords

  • Basic (laboratory) research
  • autoimmunity, fibrosis
  • lung transplantation
  • pulmonology
  • science

Fingerprint

Dive into the research topics of 'Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation'. Together they form a unique fingerprint.

Cite this