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Multimodal Single-Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis/Bladder Pain Syndrome.

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder microenvironment of patients with IC/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single-cell RNA sequencing (scRNA-seq) 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-biased response, but not Th2-biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non-Hunner-type IC (NHIC)/Hunner-type IC (HIC). M2/M2-like macrophage extends in the HIC and M1-like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro-inflammatory mediators, TNF-α, produced by tissue-resident 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-Endothelial-dominated 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.

SUBMITTER: Su F

PROVIDER: S-EPMC9218658 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose of the Meeting:Bladder pain syndrome/interstitial cystitis is a prevalent but underserved disease. At the Global Interstitial Cystitis/Bladder Pain Syndrome Society (GIBS) meeting, the organization and participants were committed to delivering word-class expertise and collaboration in research and patient care. Under the umbrella of GIBS, leading research scholars from different backgrounds and specialties, as well as clinicians, from across the globe interested in the science and art of practice of Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) were invited to deliberate on various dimensions of this disease. The meeting aimed to have global guidelines to establish firm directions to practicing clinicians and patients alike on the diagnosis and treatment of this disease entity. Chronic Pelvic Pain Syndrome (CPPS) is defined by pain in the pelvic area that can have different etiologies. This can be due to urologic, gynecologic, musculoskeletal, gastrointestinal, neurologic, and autoimmune or rheumatologic diseases. At the GIBS meeting held in Mumbai, India, in August 2019, a multidisciplinary expert panel of international urologists, gynecologists, pain specialists, and dietitians took part in a think tank to discuss the development of evidence-based diagnostic and treatment algorithms for BPS/IC. Summary of Presented Findings:The diagnosis of BPS/IC is difficult in daily clinical practice. Patients with BPS/IC present with a variety of signs and symptoms and clinical test results. Hence, they might be misdiagnosed or underdiagnosed, and the correct diagnosis might take a long time. A good history and physical examination, along with cystoscopy, is a must for the diagnosis of IC/BPS. For the treatment, besides lifestyle management and dietary advice, oral medication and bladder instillation therapy, botulinum toxin, and sacral neuromodulation were discussed. The innovation in bladder instillation applicators, as well as battery-free neuromodulation through the tibial nerve, was discussed, as well. Recommendation for Future Research:As BPS/IC is complex, for many patients, several treatments are necessary at the same time. This was presented at GIBS 2019 as the piano model. In this way, a combination of treatments is tailored to an individual patient depending on the symptoms, age, and patients' characteristics. In the art of medicine, especially when dealing with BPS/IC patients, pressing the right key at the right time makes the difference.

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Multimodal Single-Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis/Bladder Pain Syndrome.

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