PD05-07 Th1/17 POLARIZATION AND POTENTIAL TREATMENT BY AN ANTI-INTERFERON-γ DNA APTAMER IN HUNNER-TYPE INTERSTITIAL CYSTITIS

You have accessJournal of UrologyCME1 Apr 2023PD05-07 Th1/17 POLARIZATION AND POTENTIAL TREATMENT BY AN ANTI-INTERFERON-γ DNA APTAMER IN HUNNER-TYPE INTERSTITIAL CYSTITIS Yoshiyuki Akiyama, Kaori Harada, Karl Kreder, Michael O’Donnell, Maeda Daichi, Susumu Muto, Haruki Kume, Yukio Homma, and Yi Luo Yoshiyuki AkiyamaYoshiyuki Akiyama More articles by this author , Kaori HaradaKaori Harada More articles by this author , Karl KrederKarl Kreder More articles by this author , Michael O’DonnellMichael O’Donnell More articles by this author , Maeda DaichiMaeda Daichi More articles by this author , Susumu MutoSusumu Muto More articles by this author , Haruki KumeHaruki Kume More articles by this author , Yukio HommaYukio Homma More articles by this author , and Yi LuoYi Luo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To characterize unique cellular and immunological features of Hunner-type interstitial cystitis (HIC) relative to clinicopathologically similar bacillus Calmette–Guérin (BCG) cystitis, which might lead to potential therapeutic targets for treatment of HIC. METHODS: Mucosal bladder biopsies, obtained from patients with HIC (n=25) and BCG cystitis (n=13), were subjected to RNA sequencing, immunohistochemistry, and quantitative polymerase chain reaction analyses for immune cell type markers and key mediators of innate/adaptive immune responses at mRNA and /or protein levels. A mouse anti-IFN-γ aptamer, a synthetic oligo DNA sequence, was selected using the SELEX method and tested for therapeutic efficacy in a murine model of HIC which was established based on our previously developed transgenic URO-OVA mice. RESULTS: RNA sequencing identified 3,682 differentially expressed genes and 175 significantly enriched biological pathways specific to HIC, featured by upregulation of T helper (Th) 1/17-related signaling pathways, B cell-related signaling pathway, and cytosolic DNA–sensing pathway. Compared to BCG cystitis, HIC also expressed increased mRNA levels of genes involved in Th1/17-meidated immune responses, including TBX21 (a Th1 cell signature molecule), RORC (a Th17 cell signature molecule), IFNG and IL17A, as well as overexpressed IFN-γ and IL-17A proteins in the bladder (Figure 1). Intravesical instillation of the anti-IFN-γ aptamer significantly ameliorated bladder inflammation, pelvic nociception and voiding dysfunction in a HIC mouse model (Figure 2). CONCLUSIONS: Th1/17-polarization highlighted by overexpression of IFN-γ characterizes the HIC. Intravesical instillation of an anti-IFN-γ DNA aptamer is potentially useful in the treatment of human HIC. Source of Funding: This study was financially supported by the KAKENHI Grants-in-Aid from the Japanese Society for the Promotion of Science (JSPS) [grant number 22K16788] (to YA), the Japan Agency for Medical Research and Development (AMED) [JP22nk0101220] (to SM), and the National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK-111396 (to Y. Luo) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e151 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshiyuki Akiyama More articles by this author Kaori Harada More articles by this author Karl Kreder More articles by this author Michael O’Donnell More articles by this author Maeda Daichi More articles by this author Susumu Muto More articles by this author Haruki Kume More articles by this author Yukio Homma More articles by this author Yi Luo More articles by this author Expand All Advertisement PDF downloadLoading ...