Single‐cell multi‐omics analysis presents the landscape of peripheral blood T‐cell subsets in human chronic prostatitis/chronic pelvic pain syndrome

Zhang, Meng; Liu, Yi; Chen, Junyi; Chen, Lei; Meng, Jialin; Yang, Cheng; Yin, Shuiping; Zhang, Xiansheng; Zhang, Li; Hao, Zongyao; Chen, Xianguo; Liang, Chaozhao

doi:10.1111/jcmm.16021

“…Numerous studies have identified that variations in many inflammatory‐related factors (such as IL‐1β, IFN‐γ, IL‐17, etc.) could be detected in the peripheral blood serum samples of CP/CPPS patients as well as rodent EAP models 33,34 . Here, we found that HA is more highly expressed in serum samples derived from CP patients than in those derived from healthy controls, as detected by ELISA, and is positively associated with increased pain, urination symptoms, and quality of life scores on the NIH‐CPSI questionnaire.…”

Section: Discussionmentioning

confidence: 65%

4‐Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis

Chen

¹

,

Meng

²

,

Jin

³

et al. 2021

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Background Hyaluronan (HA), an extracellular matrix component, accumulates in most chronic inflammatory tissues. Here, we studied the impact of HA on the pathogenesis of chronic prostatitis. Materials and Methods First, we sorted demographic characteristics and peripheral blood serum samples from patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to assess the relationship between the levels of HA in peripheral blood serum and the severity of inflammation in patients. Second, we induced an experimental autoimmune prostatitis (EAP) mouse model and treated the mice with 4‐methylumbelliferone (4‐MU) (200 mg/kg/day). After the mice were sacrificed, RNA from Th1 cells of the mouse spleens was extracted for RNA sequencing. We used weighted gene co‐expression network analysis (WGCNA) to identify co‐expressed gene modules and hub‐gene related to the pathogenesis of EAP. The expression of critical genes associated with the identified pathway was confirmed by using western blot analysis. Results HA was significantly more highly expressed in CP/CPPS patients than in healthy volunteers and positively correlated with the severity of pain, urination symptoms, and quality of life. Besides, the protein expression of HA was significantly higher in prostate tissues derived from EAP models than in those derived from controls. 4‐MU, an oral inhibitor of HA synthesis, relieved immunocyte infiltration to the prostate and significantly reduced the proportion of Th1 cells. Based on the WGCNA, we identified 18 co‐expression modules and identified that the Grey60 and brown modules were positively associated with the EAP and negatively associated with the Control and 4‐MU‐treated groups. Pathway enrichment analyses and western blot assays proved that HA potentially activated the cell cycle pathway, increasing the proportion of Th1 cells promoting chronic prostatitis pathogenesis, while these processes were reversed by 4‐MU treatment. Conclusions Our results suggest that HA is elevated in patients with CP/CPPS compared with healthy controls and that targeting HA through 4‐MU suppresses the activity of the cell cycle‐related pathway, potentially by decreasing the proportion of Th1 cells and relieving chronic prostatitis. Our findings might inspire the clinical treatment of chronic prostatitis.

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“…ese fourteen OTUs explain the difference in the microbiota of prostatitis-like symptoms and fertile men: Burkholderiaceae, Achromobacter, Aerococcus, Blautia, Burkholderiales, Propionibacterium, Betaproteobacteria, Haemophilus, Burkholderia, Massilia, Rhizobiaceae, and Neorhizobium. In general, they are little-known microorganisms in the clinical Advances in Urology field, so sequencing is a powerful tool that allows us to discover the world surrounding enigmatic infectious diseases such as prostatitis [26][27][28]. Culture-based studies detected fewer anaerobic bacteria than NGS [10].…”

Section: Discussionmentioning

confidence: 99%

Microbiota, Prostatitis, and Fertility: Bacterial Diversity as a Possible Health Ally

Suárez

¹

,

Maya

²

2021

Advances in Urology

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Background. In health, microorganisms have been associated with the disease, although the current knowledge shows that the microbiota present in various anatomical sites is associated with multiple benefits. Objective. This study aimed to evaluate and compare the genitourinary microbiota of chronic prostatitis symptoms patients and fertile men. Materials and Methods. In this preliminary study, ten volunteers have included 5 volunteers with symptoms of chronic prostatitis (prostatitis group) and five fertile volunteers, asymptomatic for urogenital infections (control group) matched by age. Bacterial diversity analysis was performed using the 16S molecular marker to compare the microbiota present in urine and semen samples from chronic prostatitis symptoms and fertile volunteers. Seminal quality, nitric oxide levels, and seminal and serum concentration of proinflammatory cytokines were quantified. Results. Fertile men present a greater variety of operational taxonomical units-OTUs in semen (67.5%) and urine (17.6%) samples than chronic prostatitis symptoms men. Chronic prostatitis symptoms men presented a higher concentration of IL-12p70 in seminal plasma. No statistically significant differences were observed in conventional and functional seminal parameters. The species diversity in semen samples was similar in healthy men than prostatitis patients, inverted Simpson index median 5.3 (5.0–10.7) vs. 4.5 (2.1–7.8, p = 0.1508 ). Nevertheless, the microbiota present in the semen and urine samples of fertile men presents more OTUs. Less microbial diversity could be associated with chronic prostatitis symptoms. The presence of bacteria in the genitourinary tract is not always associated with the disease. Understanding the factors that affect the microbiota can implement lifestyle habits that prevent chronic prostatitis. Conclusion. Chronic prostatitis does not seem to affect male fertility; however, studies with a larger sample size are required. Our preliminary results strengthen the potential role; the greater bacterial diversity is a protective factor for chronic prostatitis.

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“…[ 12 , 29 , 30 ]. Based on the important effects of IFN- γ in EAP and CP/CPPS [ 9 – 11 ], we determined the effects of genetic polymorphisms of IFNG and IFNGR1 in CP/CPPS. Initially, functional annotation of the 8 genotyped SNPs of IFNG and IFNGR1 was performed by GTEx database, RegulomeDB, and HaploReg tools, which indicated that these 8 SNPs might have regulatory effects in human whole blood.…”

Section: Discussionmentioning

confidence: 99%

“…[12,29,30]. Based on the important effects of IFN-γ in EAP and CP/CPPS [9][10][11], we determined the effects of genetic polymorphisms of IFNG The results of codominant and log-additive models showed that rs2069718 in IFNG was correlated with the elevated CP/CPPS risk, and rs10457655 in IFNGR1 was correlated with increased NIH-CPSI score. Combined with the autoimmune characteristics of CP/CPPS and the roles of rs2069718 and rs10457655 in inflammatory diseases [30][31][32], we speculated that rs2069718 and rs10457655 might be involved in the pathogenesis of CP/CPPS through other mechanisms as predicted by the HaploReg tool [20], including protein 7 Disease Markers binding and regulatory motif alterations.…”

Section: Discussionmentioning

confidence: 99%

“…For CP/CPPS patients, IFN- γ levels were upregulated in the seminal plasma, and prostate antigen-specific IFN- γ -secreting lymphocytes were identified in the peripheral blood [ 10 ]. In our previous studies, the proportion of IFN- γ + -T-helper 1 (Th1) cells was reported to increase in the periphery blood of CP/CPPS patients [ 11 ]. Thus, IFN- γ significantly affected the pathogenesis of CP/CPPS.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Polymorphisms of IFNG, IFNGR1, and Androgen Receptor and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Chinese Han Population

Chen

¹

,

Chen

²

,

Mo

³

et al. 2021

Disease Markers

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Background. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male’s quality of life. Objective. To examine the effects of genetic polymorphisms of IFNG, IFNGR1, and androgen receptor (AR) on CP/CPPS. Methods. The single nucleotide polymorphisms (SNPs) of IFNG, IFNGR1, and AR were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the χ 2 test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence. Results. On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of IFNG, IFNGR1, and AR were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13, χ 2 = 5.37 , and P = 0.021 ) by the χ 2 test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG: crude mean difference MD = 0.98 , 95% CI: -1.71-3.67 and AA/GG: crude MD = 9.10 , 95% CI: 0.58-17.62, P = 0.10 ). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model: crude OR = 2.18 , 95% CI: 1.03-4.64, and P = 0.034 ) in patients ≥ 35 years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS. Conclusions. Genetic polymorphisms of IFNG, IFNGR1, and AR might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations.

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Single‐cell multi‐omics analysis presents the landscape of peripheral blood T‐cell subsets in human chronic prostatitis/chronic pelvic pain syndrome

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 26 publications

References 42 publications

4‐Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis

4‐Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy for chronic prostatitis

Microbiota, Prostatitis, and Fertility: Bacterial Diversity as a Possible Health Ally

Genetic Polymorphisms of IFNG, IFNGR1, and Androgen Receptor and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Chinese Han Population

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