Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.
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| Abstract |
Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.
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| Authors | Yoshiyuki Akiyama, Jian-Rong Yao, Karl J Kreder, Michael A O'Donnell, Susan K Lutgendorf, Dan Lyu, Daichi Maeda, Haruki Kume, Yukio Homma, Yi Luo |
| Journal | American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 320 Issue 2 Pg. F174-F182 (02 01 2021) ISSN: 1522-1466 [Electronic] United States |
| PMID | 33308017 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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