Journal article
Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis
iScience, Vol.26(11), 108262
11/2023
DOI: 10.1016/j.isci.2023.108262
PMCID: PMC10663743
PMID: 38026177
Abstract
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)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.
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•T helper 1/17 polarized immune responses characterize HIC inflammation•Enhanced cGAS-STING cytosolic DNA sensing pathway features HIC inflammation•Plasma cells are the key inflammatory infiltrates of the HIC bladder•Anti-IFN-γ DNA aptamer shows the therapeutic efficacy in a murine model of HIC
By conducting a comparative genome-pathological study, Akiyama and Luo et al. identified that T helper 1/17 polarization, enhanced cGAS-STING pathway and increased plasma cell infiltration are the characteristic inflammatory features of HIC and that targeting IFN-γ by a DNA aptamer holds great potential for the treatment of HIC.
Details
- Title: Subtitle
- Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis
- Creators
- Yoshiyuki Akiyama - The University of TokyoKaori Harada - TagCyx Biotechnologies (Japan)Jimpei Miyakawa - The University of TokyoKarl J. Kreder - Department of Urology, University of Iowa, Iowa City, IA, United StatesMichael A. O’Donnell - Department of Urology, University of Iowa, Iowa City, IA, United StatesMaeda Daichi - Kanazawa UniversityHiroto Katoh - The University of TokyoMiyuki Hori - TagCyx Biotechnologies (Japan)Kensuke Owari - TagCyx Biotechnologies (Japan)Kazunobu Futami - TagCyx Biotechnologies (Japan)Shumpei Ishikawa - The University of TokyoTetsuo Ushiku - The University of TokyoHaruki Kume - The University of TokyoYukio Homma - The University of TokyoYi Luo - Department of Urology, University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.26(11), 108262
- DOI
- 10.1016/j.isci.2023.108262
- PMID
- 38026177
- PMCID
- PMC10663743
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases; DOI: 10.13039/100009619, name: Japan Agency for Medical Research and Development; DOI: 10.13039/501100001691, name: Japan Society for the Promotion of Science; DOI: 10.13039/501100003478, name: Government of Japan Ministry of Health Labour and Welfare
- Language
- English
- Electronic publication date
- 10/2023
- Date published
- 11/2023
- Academic Unit
- Obstetrics and Gynecology; Urology
- Record Identifier
- 9984500247002771
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