Th1/17 polarization and potential treatment by an anti-interferon-? DNA aptamer in Hunner-type interstitial cystitis

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette–Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 polarized immune responses accompanied by prominent overexpression of interferon (IFN)-?, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a novel mouse anti-IFN-? DNA aptamer and observed that intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed novel murine HIC mouse model with little migration into the blood. Our study provides the plausible basis for clinical translation of the anti-IFN-? DNA aptamer in the treatment of human HIC. Overall design: For 25 patients with HIC, paired cold-cup biopsy samples, one from a Hunner lesion and one from a background mucosal area without Hunner lesion, were obtained. For 13 patients with BCG, one cold-cup biopsy sample was obtained from a reddened mucosal flat lesion resembling a Hunner lesion. Biopsy samples were immediately frozen in liquid nitrogen and stored at -80°C for RNA extraction. We performed RNA-seq using these samples for comparative gene expression analyses of Hunner-type interstitial cystitis (lesion and non-lesion) and BCG cystitis.