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Mass cytometry reveals species-specific differences and a new level of complexity for immune cells in the prostate.

ABSTRACT: Chronic inflammation in the benign prostate has been associated with a higher risk of developing prostate cancer. While a range of immune lineages is found in the prostate including T cells, B cells and myeloid cells, the specific subsets of immune cells with each major lineage have not been well described. In this study, we use mass cytometry (CyTOF) to comprehensively and reproducibly profile immune cells in mouse and human prostate. Using 4 myeloid markers (CD11b, CD11c, F4/80, Ly6C) in the mouse, we identified 8 phenotypically-distinct myeloid populations, demonstrating considerable heterogeneity within the immune compartment of the mouse prostate. We then profiled the prostate immune microenvironment from 9 human patients. Unlike the mouse prostate which is myeloid-dominant, the immune compartment in the benign human prostate is consistently T-lymphocyte-dominant. Using the X-shift algorithm to identify individual immune subsets based on marker expression, we found 57 phenotypically-distinct immune cell types in the human prostate. Despite similar proportions of T, B and myeloid lineage cells in the benign human prostate of all patients evaluated, we observed considerable interpatient heterogeneity in the abundance of more specific immune subsets. These findings highlight the importance of studying the immune compartment in the prostate at a granular level and will lead to future studies addressing the functional role of specific immune subsets in prostate epithelial transformation.

SUBMITTER: Fox JJ

PROVIDER: S-EPMC6734036 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Mass cytometry reveals species-specific differences and a new level of complexity for immune cells in the prostate.

Fox Jonathan J JJ Navarro Héctor I HI Hashimoto Takao T Garcia Alejandro J AJ Goldstein Andrew S AS

American journal of clinical and experimental urology 20190815 4

Chronic inflammation in the benign prostate has been associated with a higher risk of developing prostate cancer. While a range of immune lineages is found in the prostate including T cells, B cells and myeloid cells, the specific subsets of immune cells with each major lineage have not been well described. In this study, we use mass cytometry (CyTOF) to comprehensively and reproducibly profile immune cells in mouse and human prostate. Using 4 myeloid markers (CD11b, CD11c, F4/80, Ly6C) in the m ...[more]

PMID: 31511834

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Project description:IntroductionDiabetic ocular complications include sight-threatening consequences and decreased corneal sensitivity, characterized by decreased tear production, corneal sensitivity and delayed corneal epithelial wound healing. The pathogenesis of diabetic corneal disorders remains largely unknown. Growing evidence implies the participation of immune cells in the development of diabetic corneal diseases. Nonetheless, the immunological changes that result in diabetic corneal problems are largely unknown.MethodsMass cytometry by time of flight (CyTOF) was used to investigate immune cell cluster alterations associated with diabetic corneal disorders. CyTOF test was performed on corneal cells at a single level from 21-week-old diabetic (db/db) and non-diabetic (db/m) mice. A panel of 41 immune-related markers monitored different immune cell types in diabetic corneas. To investigate the proportion of each immune cell subpopulation, an unsupervised clustering method was employed, and T-distributed stochastic neighbor embedding was used to visualize the distinctions between different immune cell subsets.ResultsThrough CyTOF test, we identified 10 immune cell subsets in the corneal tissues. In a novel way, we discovered significant immune alterations in diabetic corneas, including pronounced alterations in T cells and myeloid cell subgroups in diabetic corneas linked to potential biomarkers, including CD103, CCR2, SiglecF, Ly6G, and CD172a. Comprehensive immunological profiling indicated remarkable changes in the immune microenvironment in diabetic corneas, characterized by a notable decrease in CD103+CD8+ tissue-resident memory T (TRM) cells and Tregs, as well as a dramatic increase of γδT cells and subsets of CD11b+Ly6G+ myeloid-derived suppressor cells (MDSCs).ConclusionCyTOF analysis revealed significant alterations in the immune microenvironment during the development of diabetic corneal complications. This study mapped the immune microenvironment landscape of type 2 diabetic corneas, providing a fundamental understanding of immune-driven diabetic corneal disorders.

Dataset Information

Mass cytometry reveals species-specific differences and a new level of complexity for immune cells in the prostate.

Publications

Mass cytometry reveals species-specific differences and a new level of complexity for immune cells in the prostate.

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