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The bladder microenvironment of patients with IC\/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single\u2010cell RNA sequencing (scRNA\u2010seq) and image mass cytometry (IMC) are applied to bladder biopsies of the IC\/BPS cohort. A total of 42 distinct cell clusters are identified from different groups. The increased hyperactivated Th1\u2010biased response, but not Th2\u2010biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non\u2010Hunner\u2010type IC (NHIC)\/Hunner\u2010type IC (HIC). M2\/M2\u2010like macrophage extends in the HIC and M1\u2010like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro\u2010inflammatory mediators, TNF\u2010\u03b1, produced by tissue\u2010resident macrophages and IL6, by the inflammatory fibroblasts are identified as key mediators of IC\/BPS pathogenesis. Additionally, a regulatory network between different cell types is observed as a shift from structural cell communication in unaffected normal bladder to a Macrophage\u2010Endothelial\u2010dominated interactome in NHIC\/HIC. The results demonstrate the high heterogeneity in NHIC\/HIC, and provide an essential resource for diagnosis, and treatment of IC\/BPS in the future by highlighting the importance of the microenvironment of bladder mucosa.<\/jats:p>","DOI":"10.1002\/advs.202106063","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T22:20:26Z","timestamp":1650925226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Multimodal Single\u2010Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis\/Bladder Pain Syndrome"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-4651","authenticated-orcid":false,"given":"Fei","family":"Su","sequence":"first","affiliation":[{"name":"Clinical Biobank Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences  Beijing 100730 P. 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