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*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Lung Transplantation
Autoantigens
Tubulin
Fibrosis
Inflammation
Collagen
Antibodies
Lung
Graft Rejection
Epitopes
Self Tolerance
Isoantigens
Interleukin-17
Humoral Immunity
Cellular Immunity
Interferons
T-Lymphocytes
Transplants

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Subramanian, V. ; Ramachandran, S. ; Banan, B. ; Bharat, A. ; Wang, X. ; Benshoff, N. ; Kreisel, D. ; Gelman, A. E. ; Mohanakumar, T. / Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation. In: American Journal of Transplantation. 2014 ; Vol. 14, No. 10. pp. 2359-2366.
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Subramanian, V, Ramachandran, S, Banan, B, Bharat, A, Wang, X, Benshoff, N, Kreisel, D, Gelman, AE & Mohanakumar, T 2014, 'Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation', American Journal of Transplantation, vol. 14, no. 10, pp. 2359-2366. https://doi.org/10.1111/ajt.12908

Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation. / Subramanian, V.; Ramachandran, S.; Banan, B.; Bharat, A.; Wang, X.; Benshoff, N.; Kreisel, D.; Gelman, A. E.; Mohanakumar, T.

In: American Journal of Transplantation, Vol. 14, No. 10, 01.10.2014, p. 2359-2366.

Research output: Contribution to journalArticle

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T1 - Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation

AU - Subramanian, V.

AU - Ramachandran, S.

AU - Banan, B.

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AU - Wang, X.

AU - Benshoff, N.

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AU - Mohanakumar, T.

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