PLoS ONE (Jan 2013)

Uroplakin peptide-specific autoimmunity initiates interstitial cystitis/painful bladder syndrome in mice.

  • Kenan Izgi,
  • Cengiz Z Altuntas,
  • Fuat Bicer,
  • Ahmet Ozer,
  • Cagri Sakalar,
  • Xiaoxia Li,
  • Vincent K Tuohy,
  • Firouz Daneshgari

DOI
https://doi.org/10.1371/journal.pone.0072067
Journal volume & issue
Vol. 8, no. 8
p. e72067

Abstract

Read online

The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) is enigmatic. Autoimmunity and impaired urothelium might lead the underlying pathology. A major shortcoming in IC/PBS research has been the lack of an appropriate animal model. In this study, we show that the bladder specific uroplakin 3A-derived immunogenic peptide UPK3A 65-84, which contains the binding motif for IA(d) MHC class II molecules expressed in BALB/c mice, is capable of inducing experimental autoimmune cystitis in female mice of that strain. A highly antigen-specific recall proliferative response of lymph node cells to UPK3A 65-84 was observed, characterized by selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype, including enhanced production of interferon γ and interleukin-2. T cell infiltration of the bladder and bladder-specific increased gene expression of inflammatory cytokines were observed. Either active immunization with UPK3A 65-84 or adoptive transfer of peptide-activated CD4+ T cells induced all of the predominant IC/PBS phenotypic characteristics, including increased micturition frequency, decreased urine output per micturition, and increased pelvic pain responses to stimulation with von Frey filaments. Our study demonstrates the creation of a more specific experimental autoimmune cystitis model that is the first inducible model for IC/PBS that manifests all of the major symptoms of this debilitating condition.